rs5974

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000128.4(F11):c.801A>G(p.Thr267Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,613,478 control chromosomes in the GnomAD database, including 18,011 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2147 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15864 hom. )

Consequence

F11
NM_000128.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.38

Publications

24 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 Gene-Disease associations (from GenCC):

congenital factor XI deficiency
Inheritance: AD, AR, SD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

F11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.013).

BP6

Variant 4-186280057-A-G is Benign according to our data. Variant chr4-186280057-A-G is described in ClinVar as [Benign]. Clinvar id is 255181.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.38 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F11	NM_000128.4 link	c.801A>G	p.Thr267Thr	synonymous_variant	Exon 8 of 15	ENST00000403665.7	NP_000119.1	P03951-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F11	ENST00000403665.7 link	c.801A>G	p.Thr267Thr	synonymous_variant	Exon 8 of 15	1	NM_000128.4	ENSP00000384957.2		P03951-1
F11	ENST00000452239.1 link	c.246A>G	p.Thr82Thr	synonymous_variant	Exon 3 of 6	5		ENSP00000397401.1		H0Y596

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24525

AN:

152046

Hom.:

2149

Cov.:

show subpopulations

Gnomad AFR

AF:

0.210

Gnomad AMI

AF:

0.220

Gnomad AMR

AF:

0.122

Gnomad ASJ

AF:

0.149

Gnomad EAS

AF:

0.0416

Gnomad SAS

AF:

0.204

Gnomad FIN

AF:

0.164

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.146

Gnomad OTH

AF:

0.152

GnomAD2 exomes

AF:

0.146

AC:

36722

AN:

251312

AF XY:

0.150

show subpopulations

Gnomad AFR exome

AF:

0.219

Gnomad AMR exome

AF:

0.104

Gnomad ASJ exome

AF:

0.160

Gnomad EAS exome

AF:

0.0459

Gnomad FIN exome

AF:

0.161

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.143

GnomAD4 exome

AF:

0.143

AC:

209672

AN:

1461314

Hom.:

15864

Cov.:

AF XY:

0.146

AC XY:

106230

AN XY:

726990

show subpopulations

African (AFR)

AF:

0.219

AC:

7328

AN:

33456

American (AMR)

AF:

0.107

AC:

4763

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.159

AC:

4162

AN:

26128

East Asian (EAS)

AF:

0.0478

AC:

1897

AN:

39698

South Asian (SAS)

AF:

0.204

AC:

17606

AN:

86242

European-Finnish (FIN)

AF:

0.162

AC:

8634

AN:

53416

Middle Eastern (MID)

AF:

0.193

AC:

1112

AN:

5766

European-Non Finnish (NFE)

AF:

0.140

AC:

155199

AN:

1111504

Other (OTH)

AF:

0.149

AC:

8971

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

9553

19105

28658

38210

47763

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5520

11040

16560

22080

27600

<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:

0.161

AC:

24530

AN:

152164

Hom.:

2147

Cov.:

AF XY:

0.162

AC XY:

12083

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.210

AC:

8714

AN:

41498

American (AMR)

AF:

0.121

AC:

1855

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

516

AN:

3472

East Asian (EAS)

AF:

0.0415

AC:

215

AN:

5182

South Asian (SAS)

AF:

0.203

AC:

980

AN:

4822

European-Finnish (FIN)

AF:

0.164

AC:

1739

AN:

10584

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.146

AC:

9932

AN:

68004

Other (OTH)

AF:

0.150

AC:

316

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1026

2052

3078

4104

5130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

272

544

816

1088

1360

<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:

0.147

Hom.:

7889

Bravo

AF:

0.157

Asia WGS

AF:

0.124

AC:

437

AN:

3476

EpiCase

AF:

0.154

EpiControl

AF:

0.149

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Hereditary factor XI deficiency disease

Benign:2

Jan 13, 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. -

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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 20, 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

-0.84

CADD

Benign

0.62

(source)

DANN

Benign

0.33

PhyloP100

-1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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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