NM_001992.5:c.89-3320A>G

Variant names:

• chr5-76728994-A-G
• rs253072
• NM_001992.5:c.89-3320A>G

Variant summary

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

The NM_001992.5(F2R):​c.89-3320A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 151,990 control chromosomes in the GnomAD database, including 12,167 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 0.39 (12167 hom., cov: 32)
• Consequence: F2R NM_001992.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 3 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=-1.03).
• 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.89-3320A>G		intron_variant	Intron 1 of 1	ENST00000319211.5	NP_001983.2
F2R	NM_001311313.2	c.-276+161A>G		intron_variant	Intron 2 of 2		NP_001298242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F2R	ENST00000319211.5	c.89-3320A>G		intron_variant	Intron 1 of 1	1	NM_001992.5	ENSP00000321326.4

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59904 AN: 151872 Hom.: 12162 Cov.: 32

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.394 AC: 59935 AN: 151990 Hom.: 12167 Cov.: 32 AF XY: 0.393 AC XY: 29180 AN XY: 74326

African (AFR) AF: 0.440 AC: 18245 AN: 41440

American (AMR) AF: 0.298 AC: 4555 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 1238 AN: 3470

East Asian (EAS) AF: 0.553 AC: 2861 AN: 5170

South Asian (SAS) AF: 0.239 AC: 1151 AN: 4822

European-Finnish (FIN) AF: 0.385 AC: 4064 AN: 10560

Middle Eastern (MID) AF: 0.308 AC: 90 AN: 292

European-Non Finnish (NFE) AF: 0.392 AC: 26603 AN: 67938

Other (OTH) AF: 0.393 AC: 827 AN: 2102

Alfa AF: 0.394 Hom.: 9448

Bravo AF: 0.389

Asia WGS AF: 0.376 AC: 1303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.15
PhyloP100		-1.2
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: rs253072; hg19: chr5-76024819;