dbSNP rs561241: F7:c.-122T>C (chr13-113105720-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_019616.4(F7):c.-122T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,145,320 control chromosomes in the GnomAD database, including 10,679 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1257 hom., cov: 31)

Exomes 𝑓: 0.13 ( 9422 hom. )

Consequence

F7
NM_019616.4 upstream_gene

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.08

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=-0.77).

BP6

Variant 13-113105720-T-C is Benign according to our data. Variant chr13-113105720-T-C is described in ClinVar as [Benign]. Clinvar id is 1249500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F7	NM_019616.4 link	c.-122T>C		upstream_gene_variant		ENST00000346342.8	NP_062562.1	P08709-2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
F7	ENST00000346342.8 link	c.-122T>C	upstream_gene_variant	1	NM_019616.4	ENSP00000329546.4	P08709-2
F7	ENST00000375581.3 link	c.-122T>C	upstream_gene_variant	1		ENSP00000364731.3	P08709-1
F7	ENST00000541084.5 link	c.-122T>C	upstream_gene_variant	2		ENSP00000442051.2	F5H8B0
F7	ENST00000444337.1 link	n.-122T>C	upstream_gene_variant	5		ENSP00000387669.1	E9PH36

Frequencies

GnomAD3 genomes

AF:

0.124

AC:

18803

AN:

152062

Hom.:

1256

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.0391

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.0758

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.121

Gnomad OTH

AF:

0.141

GnomAD4 exome

AF:

0.127

AC:

125838

AN:

993142

Hom.:

9422

AF XY:

0.133

AC XY:

66896

AN XY:

502786

show subpopulations

Gnomad4 AFR exome

AF:

0.135

Gnomad4 AMR exome

AF:

0.119

Gnomad4 ASJ exome

AF:

0.182

Gnomad4 EAS exome

AF:

0.0501

Gnomad4 SAS exome

AF:

0.271

Gnomad4 FIN exome

AF:

0.0785

Gnomad4 NFE exome

AF:

0.116

Gnomad4 OTH exome

AF:

0.132

GnomAD4 genome

AF:

0.124

AC:

18811

AN:

152178

Hom.:

1257

Cov.:

AF XY:

0.124

AC XY:

9225

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.127

Gnomad4 AMR

AF:

0.121

Gnomad4 ASJ

AF:

0.192

Gnomad4 EAS

AF:

0.0392

Gnomad4 SAS

AF:

0.266

Gnomad4 FIN

AF:

0.0758

Gnomad4 NFE

AF:

0.121

Gnomad4 OTH

AF:

0.139

Alfa

AF:

0.0999

Hom.:

297

Bravo

AF:

0.126

Asia WGS

AF:

0.149

AC:

518

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 17292373) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.2

DANN

Benign

0.88

Splicing

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