rs6046

Positions:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1

The NM_019616.4(F7):c.1172G>A(p.Arg391Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,612,500 control chromosomes in the GnomAD database, including 12,920 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1175 hom., cov: 33)

Exomes 𝑓: 0.12 ( 11745 hom. )

Consequence

F7
NM_019616.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: -0.0900

Variant links:

Genes affected

F7 (HGNC:3544): (coagulation factor VII) This gene encodes coagulation factor VII which is a vitamin K-dependent factor essential for hemostasis. This factor circulates in the blood in a zymogen form, and is converted to an active form by either factor IXa, factor Xa, factor XIIa, or thrombin by minor proteolysis. Upon activation of the factor VII, a heavy chain containing a catalytic domain and a light chain containing 2 EGF-like domains are generated, and two chains are held together by a disulfide bond. In the presence of factor III and calcium ions, the activated factor then further activates the coagulation cascade by converting factor IX to factor IXa and/or factor X to factor Xa. Defects in this gene can cause coagulopathy. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing to generate mature polypeptides. [provided by RefSeq, Aug 2015]

F7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

PM1

In a strand (size 4) in uniprot entity FA7_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_019616.4

BP4

Computational evidence support a benign effect (MetaRNN=0.003981173).

BP6

Variant 13-113118845-G-A is Benign according to our data. Variant chr13-113118845-G-A is described in ClinVar as [Benign]. Clinvar id is 12080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-113118845-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F7	NM_019616.4 linkuse as main transcript	c.1172G>A	p.Arg391Gln	missense_variant	8/8	ENST00000346342.8	NP_062562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F7	ENST00000346342.8 linkuse as main transcript	c.1172G>A	p.Arg391Gln	missense_variant	8/8	1	NM_019616.4	ENSP00000329546	P2	P08709-2
F7	ENST00000375581.3 linkuse as main transcript	c.1238G>A	p.Arg413Gln	missense_variant	9/9	1		ENSP00000364731	A2	P08709-1
F7	ENST00000541084.5 linkuse as main transcript	c.986G>A	p.Arg329Gln	missense_variant	6/6	2		ENSP00000442051

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17693

AN:

152072

Hom.:

1172

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.116

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.0476

Gnomad SAS

AF:

0.273

Gnomad FIN

AF:

0.0697

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.109

Gnomad OTH

AF:

0.133

GnomAD3 exomes

AF:

0.129

AC:

32014

AN:

247448

Hom.:

2706

AF XY:

0.138

AC XY:

18602

AN XY:

134762

show subpopulations

Gnomad AFR exome

AF:

0.123

Gnomad AMR exome

AF:

0.104

Gnomad ASJ exome

AF:

0.191

Gnomad EAS exome

AF:

0.0506

Gnomad SAS exome

AF:

0.281

Gnomad FIN exome

AF:

0.0703

Gnomad NFE exome

AF:

0.115

Gnomad OTH exome

AF:

0.135

GnomAD4 exome

AF:

0.116

AC:

170074

AN:

1460312

Hom.:

11745

Cov.:

AF XY:

0.122

AC XY:

88822

AN XY:

726428

show subpopulations

Gnomad4 AFR exome

AF:

0.122

Gnomad4 AMR exome

AF:

0.107

Gnomad4 ASJ exome

AF:

0.191

Gnomad4 EAS exome

AF:

0.0599

Gnomad4 SAS exome

AF:

0.276

Gnomad4 FIN exome

AF:

0.0736

Gnomad4 NFE exome

AF:

0.106

Gnomad4 OTH exome

AF:

0.124

GnomAD4 genome

AF:

0.116

AC:

17700

AN:

152188

Hom.:

1175

Cov.:

AF XY:

0.116

AC XY:

8666

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.121

Gnomad4 AMR

AF:

0.116

Gnomad4 ASJ

AF:

0.206

Gnomad4 EAS

AF:

0.0477

Gnomad4 SAS

AF:

0.274

Gnomad4 FIN

AF:

0.0697

Gnomad4 NFE

AF:

0.109

Gnomad4 OTH

AF:

0.132

Alfa

AF:

0.118

Hom.:

1641

Bravo

AF:

0.119

TwinsUK

AF:

0.114

AC:

423

ALSPAC

AF:

0.100

AC:

387

ESP6500AA

AF:

0.117

AC:

516

ESP6500EA

AF:

0.106

AC:

914

ExAC

AF:

0.131

AC:

15853

Asia WGS

AF:

0.156

AC:

543

AN:

3478

EpiCase

AF:

0.126

EpiControl

AF:

0.126

ClinVar

Significance: Benign

Submissions summary: Benign:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 19, 2024	See Variant Classification Assertion Criteria. -

Factor VII deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Factor X deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Myocardial infarction, decreased susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Sep 14, 2000

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.39

CADD

Benign

8.9

DANN

Benign

0.94

DEOGEN2

Benign

0.41

.;.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.60

T;T;T

MetaRNN

Benign

0.0040

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.61

.;.;N

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.2

.;N;N

REVEL

Benign

0.19

Sift

Benign

0.23

.;T;T

Sift4G

Benign

0.17

T;T;T

Polyphen

0.25, 0.30

.;B;B

Vest4

0.085

MPC

0.22

ClinPred

0.0032

GERP RS

-4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.28

gMVP

0.42

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