rs488703

chr13-113116562-G-Achr13-113116562-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_019616.4(F7):c.506-204G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,216 control chromosomes in the GnomAD database, including 1,688 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1688 hom., cov: 33)
• Consequence: F7 NM_019616.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0810

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 13-113116562-G-A is Benign according to our data. Variant chr13-113116562-G-A is described in ClinVar as [Benign]. Clinvar id is 1291650.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F7	NM_019616.4	c.506-204G>A		intron_variant		ENST00000346342.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F7	ENST00000346342.8	c.506-204G>A		intron_variant		1	NM_019616.4	P2

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20868 AN: 152098 Hom.: 1675 Cov.: 33

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.0467

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.0697

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.152

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.137 AC: 20910 AN: 152216 Hom.: 1688 Cov.: 33 AF XY: 0.137 AC XY: 10230 AN XY: 74428

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.0468

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.0697

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.151

Alfa AF: 0.115 Hom.: 663

Bravo AF: 0.141

Asia WGS AF: 0.165 AC: 575 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.5
Dann	Benign	0.68

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

Other links and lift over

dbSNP: rs488703; hg19: chr13-113770876;