chr5-76717018-G-A

Position:

• chr5-76717018-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001992.5(F2R):​c.88+623G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 151,962 control chromosomes in the GnomAD database, including 15,630 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (15630 hom., cov: 31)
• Consequence: F2R NM_001992.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139

Genes affected

F2R (HGNC:3537): (coagulation factor II thrombin receptor) Coagulation factor II receptor is a 7-transmembrane receptor involved in the regulation of thrombotic response. Proteolytic cleavage leads to the activation of the receptor. F2R is a G-protein coupled receptor family member. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F2R	NM_001992.5	c.88+623G>A		intron_variant		ENST00000319211.5	NP_001983.2
F2R	NM_001311313.2	c.-398+623G>A		intron_variant			NP_001298242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F2R	ENST00000319211.5	c.88+623G>A		intron_variant		1	NM_001992.5	ENSP00000321326	P1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65799 AN: 151844 Hom.: 15627 Cov.: 31

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.433 AC: 65803 AN: 151962 Hom.: 15630 Cov.: 31 AF XY: 0.434 AC XY: 32209 AN XY: 74244

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.706

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.463

Alfa AF: 0.504 Hom.: 32945

Bravo AF: 0.422

Asia WGS AF: 0.480 AC: 1666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.64

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: rs27135; hg19: chr5-76012843;