rs2227831

Variant names:

• chr5-76727669-A-G
• rs2227831
• NM_001992.5:c.89-4645A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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).
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3974 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F2R	NM_001992.5	c.89-4645A>G		intron_variant	Intron 1 of 1	ENST00000319211.5	NP_001983.2
F2R	NM_001311313.2	c.-397-1043A>G		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.89-4645A>G		intron_variant	Intron 1 of 1	1	NM_001992.5	ENSP00000321326.4

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

African (AFR) AF: 0.00773 AC: 321 AN: 41502

American (AMR) AF: 0.0198 AC: 303 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0283 AC: 98 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00913 AC: 44 AN: 4818

European-Finnish (FIN) AF: 0.0404 AC: 426 AN: 10546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0390 AC: 2652 AN: 67998

Other (OTH) AF: 0.0284 AC: 60 AN: 2112

Alfa AF: 0.0339 Hom.: 342

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
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism

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: rs2227831; hg19: chr5-76023494;