rs5976

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000128.4(F11):c.1839G>A(p.Glu613Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0488 in 1,614,124 control chromosomes in the GnomAD database, including 2,251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 192 hom., cov: 32)

Exomes 𝑓: 0.049 ( 2059 hom. )

Consequence

F11
NM_000128.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.330

Publications

8 publications found

Variant links:

Genes affected

F11 (HGNC:3529): (coagulation factor XI) This gene encodes coagulation factor XI of the blood coagulation cascade. This protein is present in plasma as a zymogen, which is a unique plasma coagulation enzyme because it exists as a homodimer consisting of two identical polypeptide chains linked by disulfide bonds. During activation of the plasma factor XI, an internal peptide bond is cleaved by factor XIIa (or XII) in each of the two chains, resulting in activated factor XIa, a serine protease composed of two heavy and two light chains held together by disulfide bonds. This activated plasma factor XI triggers the middle phase of the intrisic pathway of blood coagulation by activating factor IX. Defects in this factor lead to Rosenthal syndrome, a blood coagulation abnormality. [provided by RefSeq, Jul 2008]

F11 links:

F11-AS1 (HGNC:27725): (F11 antisense RNA 1)

F11-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.041).

BP6

Variant 4-186288575-G-A is Benign according to our data. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186288575-G-A is described in CliVar as Benign. Clinvar id is 255179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.33 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F11	NM_000128.4 link	c.1839G>A	p.Glu613Glu	synonymous_variant	Exon 15 of 15	ENST00000403665.7	NP_000119.1	P03951-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
F11	ENST00000403665.7 link	c.1839G>A	p.Glu613Glu	synonymous_variant	Exon 15 of 15	1	NM_000128.4	ENSP00000384957.2	P03951-1
F11-AS1	ENST00000505103.5 link	n.858C>T		non_coding_transcript_exon_variant	Exon 3 of 4	1
F11	ENST00000264691.4 link	c.438G>A	p.Glu146Glu	synonymous_variant	Exon 3 of 3	3		ENSP00000264691.4	X6R3B1
F11	ENST00000503841.1 link	n.358G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0474

AC:

7210

AN:

152176

Hom.:

191

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0406

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.0527

Gnomad ASJ

AF:

0.0815

Gnomad EAS

AF:

0.0679

Gnomad SAS

AF:

0.0807

Gnomad FIN

AF:

0.0382

Gnomad MID

AF:

0.0987

Gnomad NFE

AF:

0.0455

Gnomad OTH

AF:

0.0431

GnomAD2 exomes

AF:

0.0556

AC:

13980

AN:

251436

AF XY:

0.0567

show subpopulations

Gnomad AFR exome

AF:

0.0427

Gnomad AMR exome

AF:

0.0666

Gnomad ASJ exome

AF:

0.0813

Gnomad EAS exome

AF:

0.0704

Gnomad FIN exome

AF:

0.0389

Gnomad NFE exome

AF:

0.0460

Gnomad OTH exome

AF:

0.0564

GnomAD4 exome

AF:

0.0490

AC:

71594

AN:

1461830

Hom.:

2059

Cov.:

AF XY:

0.0502

AC XY:

36474

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.0428

AC:

1432

AN:

33474

American (AMR)

AF:

0.0654

AC:

2926

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0820

AC:

2144

AN:

26134

East Asian (EAS)

AF:

0.0813

AC:

3227

AN:

39698

South Asian (SAS)

AF:

0.0811

AC:

6992

AN:

86256

European-Finnish (FIN)

AF:

0.0383

AC:

2047

AN:

53418

Middle Eastern (MID)

AF:

0.114

AC:

660

AN:

5768

European-Non Finnish (NFE)

AF:

0.0441

AC:

49074

AN:

1111972

Other (OTH)

AF:

0.0512

AC:

3092

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

4210

8420

12631

16841

21051

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1906

3812

5718

7624

9530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0474

AC:

7222

AN:

152294

Hom.:

192

Cov.:

AF XY:

0.0484

AC XY:

3602

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0407

AC:

1691

AN:

41566

American (AMR)

AF:

0.0533

AC:

815

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0815

AC:

283

AN:

3472

East Asian (EAS)

AF:

0.0679

AC:

351

AN:

5172

South Asian (SAS)

AF:

0.0812

AC:

391

AN:

4818

European-Finnish (FIN)

AF:

0.0382

AC:

405

AN:

10612

Middle Eastern (MID)

AF:

0.0925

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0455

AC:

3096

AN:

68034

Other (OTH)

AF:

0.0421

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

349

697

1046

1394

1743

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0491

Hom.:

368

Bravo

AF:

0.0483

Asia WGS

AF:

0.0480

AC:

165

AN:

3478

EpiCase

AF:

0.0510

EpiControl

AF:

0.0502

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary factor XI deficiency disease

Benign:2

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Plasma factor XI deficiency

Benign:1

Nov 22, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over