rs2227831

Positions:

• chr5-76727669-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001992.5(F2R):​c.89-4645A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0261 in 152,126 control chromosomes in the GnomAD database, including 57 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 0.026 (57 hom., cov: 32)
• Consequence: F2R NM_001992.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.462

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).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0261 (3974/152126) while in subpopulation NFE AF= 0.039 (2652/67998). AF 95% confidence interval is 0.0378. There are 57 homozygotes in gnomad4. There are 1913 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3974 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F2R	NM_001992.5	c.89-4645A>G		intron_variant		ENST00000319211.5	NP_001983.2
F2R	NM_001311313.2	c.-397-1043A>G		intron_variant			NP_001298242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F2R	ENST00000319211.5	c.89-4645A>G		intron_variant		1	NM_001992.5	ENSP00000321326	P1

Frequencies

GnomAD3 genomes AF: 0.0261 AC: 3971 AN: 152016 Hom.: 57 Cov.: 32

Gnomad AFR AF: 0.00776

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0199

Gnomad ASJ AF: 0.0283

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00871

Gnomad FIN AF: 0.0404

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0390

Gnomad OTH AF: 0.0287

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

GnomAD4 genome AF: 0.0261 AC: 3974 AN: 152126 Hom.: 57 Cov.: 32 AF XY: 0.0257 AC XY: 1913 AN XY: 74368

Gnomad4 AFR AF: 0.00773

Gnomad4 AMR AF: 0.0198

Gnomad4 ASJ AF: 0.0283

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00913

Gnomad4 FIN AF: 0.0404

Gnomad4 NFE AF: 0.0390

Gnomad4 OTH AF: 0.0284

Alfa AF: 0.0353 Hom.: 114

Bravo AF: 0.0244

Asia WGS AF: 0.00375 AC: 13 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	0.52
DANN	Benign	0.54

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: rs2227831; hg19: chr5-76023494;