5-76721121-G-A

Variant names:

• chr5-76721121-G-A
• rs37248
• NM_001992.5:c.88+4726G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001992.5(F2R):​c.88+4726G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 152,056 control chromosomes in the GnomAD database, including 34,305 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 0.67 (34305 hom., cov: 32)
• Consequence: F2R NM_001992.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.847
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F2R	NM_001992.5	c.88+4726G>A		intron_variant	Intron 1 of 1	ENST00000319211.5	NP_001983.2
F2R	NM_001311313.2	c.-398+4726G>A		intron_variant	Intron 1 of 2		NP_001298242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F2R	ENST00000319211.5	c.88+4726G>A		intron_variant	Intron 1 of 1	1	NM_001992.5	ENSP00000321326.4

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101825 AN: 151938 Hom.: 34283 Cov.: 32

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.731

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.674

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

GnomAD4 genome AF: 0.670 AC: 101880 AN: 152056 Hom.: 34305 Cov.: 32 AF XY: 0.668 AC XY: 49634 AN XY: 74326

African (AFR) AF: 0.643 AC: 26684 AN: 41472

American (AMR) AF: 0.578 AC: 8838 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2231 AN: 3470

East Asian (EAS) AF: 0.717 AC: 3698 AN: 5160

South Asian (SAS) AF: 0.604 AC: 2914 AN: 4822

European-Finnish (FIN) AF: 0.731 AC: 7719 AN: 10558

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.701 AC: 47651 AN: 67986

Other (OTH) AF: 0.674 AC: 1421 AN: 2108

Alfa AF: 0.683 Hom.: 57537

Bravo AF: 0.660

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.46
PhyloP100		-0.85
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs37248; hg19: chr5-76016946;