rs5974

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000128.4(F11):c.801A>G(p.Thr267=) 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:6

Conservation

PhyloP100: -1.38

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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. Variant chr4-186280057-A-G is described in Lovd as [Benign].

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/exons	MANE	UniProt
F11	NM_000128.4 linkuse as main transcript	c.801A>G	p.Thr267=	synonymous_variant	8/15	ENST00000403665.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F11	ENST00000403665.7 linkuse as main transcript	c.801A>G	p.Thr267=	synonymous_variant	8/15	1	NM_000128.4	P1	P03951-1
F11	ENST00000452239.1 linkuse as main transcript	c.249A>G	p.Thr83=	synonymous_variant	3/6	5

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

GnomAD3 exomes

AF:

0.146

AC:

36722

AN:

251312

Hom.:

3029

AF XY:

0.150

AC XY:

20400

AN XY:

135832

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 SAS exome

AF:

0.206

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

Gnomad4 AFR exome

AF:

0.219

Gnomad4 AMR exome

AF:

0.107

Gnomad4 ASJ exome

AF:

0.159

Gnomad4 EAS exome

AF:

0.0478

Gnomad4 SAS exome

AF:

0.204

Gnomad4 FIN exome

AF:

0.162

Gnomad4 NFE exome

AF:

0.140

Gnomad4 OTH exome

AF:

0.149

GnomAD4 genome

AF:

0.161

AC:

24530

AN:

152164

Hom.:

2147

Cov.:

AF XY:

0.162

AC XY:

12083

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.210

Gnomad4 AMR

AF:

0.121

Gnomad4 ASJ

AF:

0.149

Gnomad4 EAS

AF:

0.0415

Gnomad4 SAS

AF:

0.203

Gnomad4 FIN

AF:

0.164

Gnomad4 NFE

AF:

0.146

Gnomad4 OTH

AF:

0.150

Alfa

AF:

0.146

Hom.:

3569

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:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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 13, 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 provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

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 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.62

DANN

Benign

0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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