13-113115754-C-T

Position:

chr13-113115754-C-T

Variant summary

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

The NM_019616.4(F7):c.459C>T(p.His153=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,613,076 control chromosomes in the GnomAD database, including 14,626 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1330 hom., cov: 33)

Exomes 𝑓: 0.13 ( 13296 hom. )

Consequence

F7
NM_019616.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.13

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 13-113115754-C-T is Benign according to our data. Variant chr13-113115754-C-T is described in ClinVar as [Benign]. Clinvar id is 255218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-113115754-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.13 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.264 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.459C>T	p.His153=	synonymous_variant	5/8	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.459C>T	p.His153=	synonymous_variant	5/8	1	NM_019616.4	ENSP00000329546	P2	P08709-2

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19248

AN:

152142

Hom.:

1328

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.122

Gnomad ASJ

AF:

0.207

Gnomad EAS

AF:

0.0472

Gnomad SAS

AF:

0.276

Gnomad FIN

AF:

0.0765

Gnomad MID

AF:

0.207

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.144

GnomAD3 exomes

AF:

0.137

AC:

34334

AN:

250174

Hom.:

2982

AF XY:

0.146

AC XY:

19798

AN XY:

135650

show subpopulations

Gnomad AFR exome

AF:

0.136

Gnomad AMR exome

AF:

0.115

Gnomad ASJ exome

AF:

0.195

Gnomad EAS exome

AF:

0.0502

Gnomad SAS exome

AF:

0.282

Gnomad FIN exome

AF:

0.0749

Gnomad NFE exome

AF:

0.126

Gnomad OTH exome

AF:

0.142

GnomAD4 exome

AF:

0.126

AC:

183916

AN:

1460816

Hom.:

13296

Cov.:

AF XY:

0.132

AC XY:

95567

AN XY:

726700

show subpopulations

Gnomad4 AFR exome

AF:

0.138

Gnomad4 AMR exome

AF:

0.118

Gnomad4 ASJ exome

AF:

0.195

Gnomad4 EAS exome

AF:

0.0580

Gnomad4 SAS exome

AF:

0.278

Gnomad4 FIN exome

AF:

0.0786

Gnomad4 NFE exome

AF:

0.116

Gnomad4 OTH exome

AF:

0.134

GnomAD4 genome

AF:

0.126

AC:

19256

AN:

152260

Hom.:

1330

Cov.:

AF XY:

0.126

AC XY:

9374

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.134

Gnomad4 AMR

AF:

0.122

Gnomad4 ASJ

AF:

0.207

Gnomad4 EAS

AF:

0.0473

Gnomad4 SAS

AF:

0.276

Gnomad4 FIN

AF:

0.0765

Gnomad4 NFE

AF:

0.120

Gnomad4 OTH

AF:

0.143

Alfa

AF:

0.129

Hom.:

1856

Bravo

AF:

0.129

Asia WGS

AF:

0.159

AC:

552

AN:

3478

EpiCase

AF:

0.136

EpiControl

AF:

0.137

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 20, 2019	- -

Factor VII deficiency

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.3

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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