Variant rs6041 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_019616.4(F7):c.740-20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,579,270 control chromosomes in the GnomAD database, including 12,714 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1211 hom., cov: 33)

Exomes 𝑓: 0.12 ( 11503 hom. )

Consequence

F7
NM_019616.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.77

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 13-113118393-G-A is Benign according to our data. Variant chr13-113118393-G-A is described in ClinVar as [Benign]. Clinvar id is 255221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-113118393-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	UniProt
F7	NM_019616.4 linkuse as main transcript	c.740-20G>A		intron_variant		ENST00000346342.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
F7	ENST00000346342.8 linkuse as main transcript	c.740-20G>A	intron_variant	1	NM_019616.4	P2	P08709-2
F7	ENST00000375581.3 linkuse as main transcript	c.806-20G>A	intron_variant	1		A2	P08709-1
F7	ENST00000541084.5 linkuse as main transcript	c.554-20G>A	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17979

AN:

152092

Hom.:

1203

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.204

Gnomad EAS

AF:

0.0474

Gnomad SAS

AF:

0.274

Gnomad FIN

AF:

0.0696

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.109

Gnomad OTH

AF:

0.136

GnomAD3 exomes

AF:

0.130

AC:

29605

AN:

227000

Hom.:

2519

AF XY:

0.139

AC XY:

17203

AN XY:

123768

show subpopulations

Gnomad AFR exome

AF:

0.130

Gnomad AMR exome

AF:

0.105

Gnomad ASJ exome

AF:

0.191

Gnomad EAS exome

AF:

0.0503

Gnomad SAS exome

AF:

0.284

Gnomad FIN exome

AF:

0.0718

Gnomad NFE exome

AF:

0.115

Gnomad OTH exome

AF:

0.134

GnomAD4 exome

AF:

0.117

AC:

166410

AN:

1427060

Hom.:

11503

Cov.:

AF XY:

0.122

AC XY:

86367

AN XY:

705972

show subpopulations

Gnomad4 AFR exome

AF:

0.130

Gnomad4 AMR exome

AF:

0.108

Gnomad4 ASJ exome

AF:

0.191

Gnomad4 EAS exome

AF:

0.0600

Gnomad4 SAS exome

AF:

0.277

Gnomad4 FIN exome

AF:

0.0747

Gnomad4 NFE exome

AF:

0.105

Gnomad4 OTH exome

AF:

0.124

GnomAD4 genome

AF:

0.118

AC:

18009

AN:

152210

Hom.:

1211

Cov.:

AF XY:

0.119

AC XY:

8822

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.128

Gnomad4 AMR

AF:

0.117

Gnomad4 ASJ

AF:

0.204

Gnomad4 EAS

AF:

0.0475

Gnomad4 SAS

AF:

0.274

Gnomad4 FIN

AF:

0.0696

Gnomad4 NFE

AF:

0.109

Gnomad4 OTH

AF:

0.134

Alfa

AF:

0.0980

Hom.:

259

Bravo

AF:

0.121

Asia WGS

AF:

0.160

AC:

556

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.8

DANN

Benign

0.80

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