rs6027

Positions:

chr1-169514323-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000367797.9(F5):c.6665A>G(p.Asp2222Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0594 in 1,612,978 control chromosomes in the GnomAD database, including 3,361 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 350 hom., cov: 32)

Exomes 𝑓: 0.060 ( 3011 hom. )

Consequence

F5
ENST00000367797.9 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 6.84

Variant links:

Genes affected

F5 (HGNC:3542): (coagulation factor V) This gene encodes an essential cofactor of the blood coagulation cascade. This factor circulates in plasma, and is converted to the active form by the release of the activation peptide by thrombin during coagulation. This generates a heavy chain and a light chain which are held together by calcium ions. The activated protein is a cofactor that participates with activated coagulation factor X to activate prothrombin to thrombin. Defects in this gene result in either an autosomal recessive hemorrhagic diathesis or an autosomal dominant form of thrombophilia, which is known as activated protein C resistance. [provided by RefSeq, Oct 2008]

F5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009426534).

BP6

Variant 1-169514323-T-C is Benign according to our data. Variant chr1-169514323-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 255215.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-169514323-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F5	NM_000130.5 linkuse as main transcript	c.6665A>G	p.Asp2222Gly	missense_variant	25/25	ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
F5	ENST00000367797.9 linkuse as main transcript	c.6665A>G	p.Asp2222Gly	missense_variant	25/25	1	NM_000130.5	ENSP00000356771	P2
F5	ENST00000367796.3 linkuse as main transcript	c.6680A>G	p.Asp2227Gly	missense_variant	25/25	5		ENSP00000356770	A2
F5	ENST00000495481.1 linkuse as main transcript	n.439A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0540

AC:

8202

AN:

152012

Hom.:

349

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0108

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.100

Gnomad ASJ

AF:

0.0750

Gnomad EAS

AF:

0.0298

Gnomad SAS

AF:

0.0725

Gnomad FIN

AF:

0.0853

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0647

Gnomad OTH

AF:

0.0637

GnomAD3 exomes

AF:

0.0641

AC:

16084

AN:

251060

Hom.:

659

AF XY:

0.0649

AC XY:

8800

AN XY:

135692

show subpopulations

Gnomad AFR exome

AF:

0.00888

Gnomad AMR exome

AF:

0.0938

Gnomad ASJ exome

AF:

0.0696

Gnomad EAS exome

AF:

0.0296

Gnomad SAS exome

AF:

0.0734

Gnomad FIN exome

AF:

0.0863

Gnomad NFE exome

AF:

0.0611

Gnomad OTH exome

AF:

0.0673

GnomAD4 exome

AF:

0.0600

AC:

87631

AN:

1460848

Hom.:

3011

Cov.:

AF XY:

0.0608

AC XY:

44201

AN XY:

726756

show subpopulations

Gnomad4 AFR exome

AF:

0.00843

Gnomad4 AMR exome

AF:

0.0940

Gnomad4 ASJ exome

AF:

0.0690

Gnomad4 EAS exome

AF:

0.0594

Gnomad4 SAS exome

AF:

0.0730

Gnomad4 FIN exome

AF:

0.0841

Gnomad4 NFE exome

AF:

0.0579

Gnomad4 OTH exome

AF:

0.0582

GnomAD4 genome

AF:

0.0539

AC:

8202

AN:

152130

Hom.:

350

Cov.:

AF XY:

0.0564

AC XY:

4198

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0108

Gnomad4 AMR

AF:

0.100

Gnomad4 ASJ

AF:

0.0750

Gnomad4 EAS

AF:

0.0298

Gnomad4 SAS

AF:

0.0723

Gnomad4 FIN

AF:

0.0853

Gnomad4 NFE

AF:

0.0648

Gnomad4 OTH

AF:

0.0630

Alfa

AF:

0.0614

Hom.:

850

Bravo

AF:

0.0499

TwinsUK

AF:

0.0515

AC:

191

ALSPAC

AF:

0.0516

AC:

199

ESP6500AA

AF:

0.00953

AC:

ESP6500EA

AF:

0.0617

AC:

531

ExAC

AF:

0.0606

AC:

7362

Asia WGS

AF:

0.0610

AC:

212

AN:

3478

EpiCase

AF:

0.0614

EpiControl

AF:

0.0625

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	This variant is associated with the following publications: (PMID: 33103541, 31399523, 22044617, 14656739, 14695293, 25896652, 20694279) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Congenital factor V deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Thrombophilia due to activated protein C resistance

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

T;T

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.78

T;T

MetaRNN

Benign

0.0094

T;T

MetaSVM

Uncertain

0.25

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

0.000068

P;P

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-5.7

D;D

REVEL

Uncertain

0.61

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.0090

D;D

Polyphen

1.0

D;.

Vest4

0.41

MPC

0.40

ClinPred

0.012

GERP RS

4.9

Varity_R

0.82

gMVP

0.79

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