rs519650

Positions:

chr13-113117603-A-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_019616.4(F7):c.739+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00395 in 1,574,426 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0025 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0041 ( 22 hom. )

Consequence

F7
NM_019616.4 splice_region, intron

Scores

Splicing: ADA: 0.001902

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.871

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 13-113117603-A-G is Benign according to our data. Variant chr13-113117603-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 402841.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2}. Variant chr13-113117603-A-G is described in Lovd as [Benign].

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F7	NM_019616.4 linkuse as main transcript	c.739+7A>G		splice_region_variant, intron_variant		ENST00000346342.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
F7	ENST00000346342.8 linkuse as main transcript	c.739+7A>G	splice_region_variant, intron_variant	1	NM_019616.4	P2	P08709-2
F7	ENST00000375581.3 linkuse as main transcript	c.805+7A>G	splice_region_variant, intron_variant	1		A2	P08709-1
F7	ENST00000541084.5 linkuse as main transcript	c.553+7A>G	splice_region_variant, intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00248

AC:

359

AN:

145020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000760

Gnomad AMI

AF:

0.00814

Gnomad AMR

AF:

0.00239

Gnomad ASJ

AF:

0.00699

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000219

Gnomad FIN

AF:

0.00441

Gnomad MID

AF:

0.00340

Gnomad NFE

AF:

0.00333

Gnomad OTH

AF:

0.000982

GnomAD3 exomes

AF:

0.00395

AC:

984

AN:

248898

Hom.:

AF XY:

0.00377

AC XY:

507

AN XY:

134606

show subpopulations

Gnomad AFR exome

AF:

0.000804

Gnomad AMR exome

AF:

0.00393

Gnomad ASJ exome

AF:

0.00954

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00102

Gnomad FIN exome

AF:

0.00285

Gnomad NFE exome

AF:

0.00551

Gnomad OTH exome

AF:

0.00526

GnomAD4 exome

AF:

0.00410

AC:

5858

AN:

1429294

Hom.:

Cov.:

AF XY:

0.00420

AC XY:

2986

AN XY:

711278

show subpopulations

Gnomad4 AFR exome

AF:

0.000692

Gnomad4 AMR exome

AF:

0.00221

Gnomad4 ASJ exome

AF:

0.00693

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.000711

Gnomad4 FIN exome

AF:

0.00479

Gnomad4 NFE exome

AF:

0.00460

Gnomad4 OTH exome

AF:

0.00401

GnomAD4 genome

AF:

0.00247

AC:

359

AN:

145132

Hom.:

Cov.:

AF XY:

0.00262

AC XY:

186

AN XY:

70892

show subpopulations

Gnomad4 AFR

AF:

0.000758

Gnomad4 AMR

AF:

0.00239

Gnomad4 ASJ

AF:

0.00699

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000220

Gnomad4 FIN

AF:

0.00441

Gnomad4 NFE

AF:

0.00333

Gnomad4 OTH

AF:

0.000972

Alfa

AF:

0.0143

Hom.:

Bravo

AF:

0.0116

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Factor VII deficiency

Uncertain:1

Uncertain significance, 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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 136/13006=1.04% -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2023

F7: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.8

DANN

Benign

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0019

dbscSNV1_RF

Benign

0.046

SpliceAI score (max)

0.31

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.31

Position offset: 30

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