rs168753

Variant names:

• chr5-76732299-A-T
• rs168753
• NM_001992.5:c.89-15A>T

Your query was ambiguous. Multiple possible variants found:

• chr5-76732299-A-T
• chr5-76732299-A-C
• chr5-76732299-A-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.89-15A>T variant causes a 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. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.14 (2063 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22417 hom.)
• Consequence: F2R NM_001992.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273
• Publications: 32 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001992.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F2R	NM_001992.5	MANE Select	c.89-15A>T		intron	N/A	NP_001983.2	P25116
	F2R	NM_001311313.2		c.-275-15A>T		intron	N/A	NP_001298242.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F2R	ENST00000319211.5	TSL:1 MANE Select	c.89-15A>T		intron	N/A	ENSP00000321326.4	P25116

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

GnomAD2 exomes AF: 0.169 AC: 34560 AN: 204256 AF XY: 0.169

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 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

African (AFR) AF: 0.0584 AC: 1791 AN: 30650

American (AMR) AF: 0.0943 AC: 3068 AN: 32520

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 2359 AN: 23202

East Asian (EAS) AF: 0.439 AC: 17174 AN: 39092

South Asian (SAS) AF: 0.106 AC: 8119 AN: 76804

European-Finnish (FIN) AF: 0.191 AC: 9770 AN: 51100

Middle Eastern (MID) AF: 0.131 AC: 709 AN: 5424

European-Non Finnish (NFE) AF: 0.170 AC: 185137 AN: 1086698

Other (OTH) AF: 0.170 AC: 9796 AN: 57750

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

African (AFR) AF: 0.0609 AC: 2524 AN: 41468

American (AMR) AF: 0.114 AC: 1745 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 363 AN: 3462

East Asian (EAS) AF: 0.468 AC: 2418 AN: 5166

South Asian (SAS) AF: 0.106 AC: 506 AN: 4796

European-Finnish (FIN) AF: 0.196 AC: 2065 AN: 10554

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11475 AN: 67974

Other (OTH) AF: 0.148 AC: 313 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.96
DANN	Benign	0.34
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: rs168753; hg19: chr5-76028124; COSMIC: COSV107397818;