5-76723491-C-T

Variant names:

• chr5-76723491-C-T
• rs37250
• NM_001992.5:c.88+7096C>T

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+7096C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,028 control chromosomes in the GnomAD database, including 8,616 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 0.31 (8616 hom., cov: 32)
• Consequence: F2R NM_001992.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F2R	NM_001992.5	c.88+7096C>T		intron_variant	Intron 1 of 1	ENST00000319211.5	NP_001983.2
F2R	NM_001311313.2	c.-397-5221C>T		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+7096C>T		intron_variant	Intron 1 of 1	1	NM_001992.5	ENSP00000321326.4

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47583 AN: 151910 Hom.: 8616 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.313 AC: 47578 AN: 152028 Hom.: 8616 Cov.: 32 AF XY: 0.313 AC XY: 23229 AN XY: 74280

African (AFR) AF: 0.149 AC: 6174 AN: 41494

American (AMR) AF: 0.269 AC: 4107 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1105 AN: 3470

East Asian (EAS) AF: 0.552 AC: 2857 AN: 5172

South Asian (SAS) AF: 0.232 AC: 1115 AN: 4814

European-Finnish (FIN) AF: 0.391 AC: 4127 AN: 10548

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.398 AC: 27017 AN: 67948

Other (OTH) AF: 0.331 AC: 699 AN: 2112

Alfa AF: 0.363 Hom.: 5750

Bravo AF: 0.296

Asia WGS AF: 0.347 AC: 1203 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	2.0
DANN	Benign	0.50
PhyloP100		-0.27
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: rs37250; hg19: chr5-76019316; COSMIC: COSV59930012;