rs9332618

Positions:

• chr1-169531243-G-A

Variant summary

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

The ENST00000367797.9(F5):​c.4972-221C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0885 in 151,934 control chromosomes in the GnomAD database, including 782 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.088 (782 hom., cov: 33)
• Consequence: F5 ENST00000367797.9 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.143

Genes affected

F5 (HGNC:3542): (coagulation factor V) This gene encodes an essential cofactor of the blood coagulation cascade. This factor circulates in plasma, and is converted to the active form by the release of the activation peptide by thrombin during coagulation. This generates a heavy chain and a light chain which are held together by calcium ions. The activated protein is a cofactor that participates with activated coagulation factor X to activate prothrombin to thrombin. Defects in this gene result in either an autosomal recessive hemorrhagic diathesis or an autosomal dominant form of thrombophilia, which is known as activated protein C resistance. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-169531243-G-A is Benign according to our data. Variant chr1-169531243-G-A is described in ClinVar as [Benign]. Clinvar id is 1287709.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F5	NM_000130.5	c.4972-221C>T		intron_variant		ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9	c.4972-221C>T		intron_variant		1	NM_000130.5	ENSP00000356771	P2
F5	ENST00000367796.3	c.4987-221C>T		intron_variant		5		ENSP00000356770	A2

Frequencies

GnomAD3 genomes AF: 0.0885 AC: 13433 AN: 151816 Hom.: 781 Cov.: 33

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0624

Gnomad ASJ AF: 0.0979

Gnomad EAS AF: 0.0385

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0861

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

GnomAD4 genome AF: 0.0885 AC: 13439 AN: 151934 Hom.: 782 Cov.: 33 AF XY: 0.0898 AC XY: 6670 AN XY: 74252

Gnomad4 AFR AF: 0.0429

Gnomad4 AMR AF: 0.0623

Gnomad4 ASJ AF: 0.0979

Gnomad4 EAS AF: 0.0382

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.0848

Alfa AF: 0.103 Hom.: 535

Bravo AF: 0.0792

Asia WGS AF: 0.0630 AC: 219 AN: 3476

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

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.0
DANN	Benign	0.57

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: rs9332618; hg19: chr1-169500481;