rs253061

Positions:

• chr5-76718175-C-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+1780C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 152,076 control chromosomes in the GnomAD database, including 42,115 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 0.74 (42115 hom., cov: 31)
• Consequence: F2R NM_001992.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.510

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F2R	NM_001992.5	c.88+1780C>A		intron_variant		ENST00000319211.5	NP_001983.2
F2R	NM_001311313.2	c.-398+1780C>A		intron_variant			NP_001298242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F2R	ENST00000319211.5	c.88+1780C>A		intron_variant		1	NM_001992.5	ENSP00000321326	P1

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112922 AN: 151958 Hom.: 42083 Cov.: 31

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.746

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

GnomAD4 genome AF: 0.743 AC: 112998 AN: 152076 Hom.: 42115 Cov.: 31 AF XY: 0.743 AC XY: 55208 AN XY: 74334

Gnomad4 AFR AF: 0.756

Gnomad4 AMR AF: 0.655

Gnomad4 ASJ AF: 0.725

Gnomad4 EAS AF: 0.741

Gnomad4 SAS AF: 0.690

Gnomad4 FIN AF: 0.795

Gnomad4 NFE AF: 0.752

Gnomad4 OTH AF: 0.745

Alfa AF: 0.745 Hom.: 71619

Bravo AF: 0.734

Asia WGS AF: 0.738 AC: 2561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.5
DANN	Benign	0.78

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: rs253061; hg19: chr5-76014000;