5-76732299-A-T

Position:

• chr5-76732299-A-T

Variant summary

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

The ENST00000319211.5(F2R):​c.89-15A>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 1,555,246 control chromosomes in the GnomAD database, including 24,480 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 0.14 (2063 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22417 hom.)
• Consequence: F2R ENST00000319211.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F2R	NM_001992.5	c.89-15A>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000319211.5	NP_001983.2
F2R	NM_001311313.2	c.-275-15A>T		splice_polypyrimidine_tract_variant, intron_variant			NP_001298242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F2R	ENST00000319211.5	c.89-15A>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001992.5	ENSP00000321326	P1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21581 AN: 151890 Hom.: 2064 Cov.: 32

Gnomad AFR AF: 0.0610

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.150

GnomAD3 exomes AF: 0.169 AC: 34560 AN: 204256 Hom.: 3865 AF XY: 0.169 AC XY: 18872 AN XY: 111770

Gnomad AFR exome AF: 0.0632

Gnomad AMR exome AF: 0.0911

Gnomad ASJ exome AF: 0.101

Gnomad EAS exome AF: 0.469

Gnomad SAS exome AF: 0.104

Gnomad FIN exome AF: 0.192

Gnomad NFE exome AF: 0.171

Gnomad OTH exome AF: 0.164

GnomAD4 exome AF: 0.170 AC: 237923 AN: 1403240 Hom.: 22417 Cov.: 30 AF XY: 0.168 AC XY: 116650 AN XY: 695070

Gnomad4 AFR exome AF: 0.0584

Gnomad4 AMR exome AF: 0.0943

Gnomad4 ASJ exome AF: 0.102

Gnomad4 EAS exome AF: 0.439

Gnomad4 SAS exome AF: 0.106

Gnomad4 FIN exome AF: 0.191

Gnomad4 NFE exome AF: 0.170

Gnomad4 OTH exome AF: 0.170

GnomAD4 genome AF: 0.142 AC: 21574 AN: 152006 Hom.: 2063 Cov.: 32 AF XY: 0.144 AC XY: 10730 AN XY: 74278

Gnomad4 AFR AF: 0.0609

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.148

Alfa AF: 0.142 Hom.: 361

Bravo AF: 0.134

Asia WGS AF: 0.240 AC: 832 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.96
DANN	Benign	0.34

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: rs168753; hg19: chr5-76028124;