rs5976

Positions:

chr4-186288575-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000128.4(F11):c.1839G>A(p.Glu613=) 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

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 made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 4-186288575-G-A is Benign according to our data. Variant chr4-186288575-G-A is described in ClinVar 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 Lovd as [Benign].

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/exons	MANE	Protein	UniProt
F11	NM_000128.4 linkuse as main transcript	c.1839G>A	p.Glu613=	synonymous_variant	15/15	ENST00000403665.7	NP_000119.1
F11-AS1	NR_033900.1 linkuse as main transcript	n.919C>T		non_coding_transcript_exon_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F11	ENST00000403665.7 linkuse as main transcript	c.1839G>A	p.Glu613=	synonymous_variant	15/15	1	NM_000128.4	ENSP00000384957	P1	P03951-1
F11-AS1	ENST00000505103.5 linkuse as main transcript	n.858C>T		non_coding_transcript_exon_variant	3/4	1
F11	ENST00000264691.4 linkuse as main transcript	c.441G>A	p.Glu147=	synonymous_variant	3/3	3		ENSP00000264691
F11	ENST00000503841.1 linkuse as main transcript	n.358G>A		non_coding_transcript_exon_variant	2/2	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

GnomAD3 exomes

AF:

0.0556

AC:

13980

AN:

251436

Hom.:

458

AF XY:

0.0567

AC XY:

7699

AN XY:

135890

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 SAS exome

AF:

0.0799

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

Gnomad4 AFR exome

AF:

0.0428

Gnomad4 AMR exome

AF:

0.0654

Gnomad4 ASJ exome

AF:

0.0820

Gnomad4 EAS exome

AF:

0.0813

Gnomad4 SAS exome

AF:

0.0811

Gnomad4 FIN exome

AF:

0.0383

Gnomad4 NFE exome

AF:

0.0441

Gnomad4 OTH exome

AF:

0.0512

GnomAD4 genome

AF:

0.0474

AC:

7222

AN:

152294

Hom.:

192

Cov.:

AF XY:

0.0484

AC XY:

3602

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0407

Gnomad4 AMR

AF:

0.0533

Gnomad4 ASJ

AF:

0.0815

Gnomad4 EAS

AF:

0.0679

Gnomad4 SAS

AF:

0.0812

Gnomad4 FIN

AF:

0.0382

Gnomad4 NFE

AF:

0.0455

Gnomad4 OTH

AF:

0.0421

Alfa

AF:

0.0487

Hom.:

270

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Hereditary factor XI deficiency disease

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Plasma factor XI deficiency

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Nov 22, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over