rs5970

Positions:

chr4-186284147-T-C

Variant summary

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

The NM_000128.4(F11):c.1191T>C(p.Gly397=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,614,012 control chromosomes in the GnomAD database, including 18,427 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2152 hom., cov: 33)

Exomes 𝑓: 0.15 ( 16275 hom. )

Consequence

F11
NM_000128.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.76

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=-0.92).

BP6

Variant 4-186284147-T-C is Benign according to our data. Variant chr4-186284147-T-C is described in ClinVar as [Benign]. Clinvar id is 255176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186284147-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.76 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.205 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.1191T>C	p.Gly397=	synonymous_variant	11/15	ENST00000403665.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F11	ENST00000403665.7 linkuse as main transcript	c.1191T>C	p.Gly397=	synonymous_variant	11/15	1	NM_000128.4	P1	P03951-1

Frequencies

GnomAD3 genomes

AF:

0.162

AC:

24646

AN:

152018

Hom.:

2154

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.220

Gnomad AMR

AF:

0.123

Gnomad ASJ

AF:

0.152

Gnomad EAS

AF:

0.0407

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.165

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.153

GnomAD3 exomes

AF:

0.149

AC:

37471

AN:

251486

Hom.:

3147

AF XY:

0.154

AC XY:

20884

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.217

Gnomad AMR exome

AF:

0.105

Gnomad ASJ exome

AF:

0.163

Gnomad EAS exome

AF:

0.0458

Gnomad SAS exome

AF:

0.221

Gnomad FIN exome

AF:

0.161

Gnomad NFE exome

AF:

0.147

Gnomad OTH exome

AF:

0.148

GnomAD4 exome

AF:

0.145

AC:

212034

AN:

1461876

Hom.:

16275

Cov.:

AF XY:

0.148

AC XY:

107828

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.218

Gnomad4 AMR exome

AF:

0.108

Gnomad4 ASJ exome

AF:

0.162

Gnomad4 EAS exome

AF:

0.0476

Gnomad4 SAS exome

AF:

0.220

Gnomad4 FIN exome

AF:

0.162

Gnomad4 NFE exome

AF:

0.140

Gnomad4 OTH exome

AF:

0.151

GnomAD4 genome

AF:

0.162

AC:

24652

AN:

152136

Hom.:

2152

Cov.:

AF XY:

0.163

AC XY:

12138

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.209

Gnomad4 AMR

AF:

0.123

Gnomad4 ASJ

AF:

0.152

Gnomad4 EAS

AF:

0.0406

Gnomad4 SAS

AF:

0.215

Gnomad4 FIN

AF:

0.165

Gnomad4 NFE

AF:

0.147

Gnomad4 OTH

AF:

0.151

Alfa

AF:

0.152

Hom.:

2383

Bravo

AF:

0.158

Asia WGS

AF:

0.130

AC:

458

AN:

3478

EpiCase

AF:

0.157

EpiControl

AF:

0.152

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 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 provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	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

-0.92

CADD

Benign

0.022

DANN

Benign

0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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