chr5-76716336-C-T

Variant names:

• chr5-76716336-C-T
• rs1748341585
• NM_001992.5:c.29C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001992.5(F2R):​c.29C>T​(p.Ala10Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: F2R NM_001992.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.615
• Publications: 0 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]

ENSG00000225407 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10668644).

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.29C>T	p.Ala10Val	missense	Exon 1 of 2	NP_001983.2	P25116
	F2R	NM_001311313.2		c.-457C>T		5_prime_UTR	Exon 1 of 3	NP_001298242.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F2R	ENST00000319211.5	TSL:1 MANE Select	c.29C>T	p.Ala10Val	missense	Exon 1 of 2	ENSP00000321326.4	P25116
	F2R	ENST00000505600.1	TSL:2	c.29C>T	p.Ala10Val	missense	Exon 1 of 2	ENSP00000426398.1	G3XAL6
	ENSG00000225407	ENST00000507514.1	TSL:3	n.-121G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.80e-7 AC: 1 AN: 1282092 Hom.: 0 Cov.: 31 AF XY: 0.00000160 AC XY: 1 AN XY: 624536

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26156

American (AMR) AF: 0.00 AC: 0 AN: 21900

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21576

East Asian (EAS) AF: 0.00 AC: 0 AN: 28664

South Asian (SAS) AF: 0.00 AC: 0 AN: 65704

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5182

European-Non Finnish (NFE) AF: 9.74e-7 AC: 1 AN: 1027186

Other (OTH) AF: 0.00 AC: 0 AN: 53416

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.63	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.61
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.11
Sift	Uncertain	0.015	D
Sift4G	Benign	0.12	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.32		Gain of helix (P = 0.027)
MVP		0.66
MPC		1.9
ClinPred		0.13	T
GERP RS		1.4
PromoterAI		-0.23	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.043
gMVP		0.50
Mutation Taster		=88/12	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: rs1748341585; hg19: chr5-76012161;