rs11563071

Positions:

• chr2-234006896-C-G
• chr2-234006896-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The ENST00000324695.9(TRPM8):​c.3174C>G​(p.Val1058=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0997 in 1,611,872 control chromosomes in the GnomAD database, including 8,726 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 0.12 (1236 hom., cov: 32)
  • Exomes 𝑓: 0.098 (7490 hom.)
• Consequence: TRPM8 ENST00000324695.9 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75

Genes affected

TRPM8 (HGNC:17961): (transient receptor potential cation channel subfamily M member 8) Predicted to enable ligand-gated calcium channel activity. Predicted to be involved in calcium ion transmembrane transport and positive regulation of cold-induced thermogenesis. Predicted to act upstream of or within several processes, including cellular calcium ion homeostasis; response to cold; and thermoception. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=1.75 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM8	NM_024080.5	c.3174C>G	p.Val1058=	synonymous_variant	23/26	ENST00000324695.9	NP_076985.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM8	ENST00000324695.9	c.3174C>G	p.Val1058=	synonymous_variant	23/26	1	NM_024080.5	ENSP00000323926	P1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18103 AN: 151976 Hom.: 1233 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0775

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0833

Gnomad FIN AF: 0.0839

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0929

Gnomad OTH AF: 0.114

GnomAD3 exomes AF: 0.104 AC: 26096 AN: 251164 Hom.: 1492 AF XY: 0.0993 AC XY: 13484 AN XY: 135744

Gnomad AFR exome AF: 0.185

Gnomad AMR exome AF: 0.146

Gnomad ASJ exome AF: 0.0794

Gnomad EAS exome AF: 0.109

Gnomad SAS exome AF: 0.0819

Gnomad FIN exome AF: 0.0833

Gnomad NFE exome AF: 0.0913

Gnomad OTH exome AF: 0.0939

GnomAD4 exome AF: 0.0977 AC: 142609 AN: 1459778 Hom.: 7490 Cov.: 30 AF XY: 0.0966 AC XY: 70177 AN XY: 726334

Gnomad4 AFR exome AF: 0.181

Gnomad4 AMR exome AF: 0.143

Gnomad4 ASJ exome AF: 0.0765

Gnomad4 EAS exome AF: 0.105

Gnomad4 SAS exome AF: 0.0837

Gnomad4 FIN exome AF: 0.0838

Gnomad4 NFE exome AF: 0.0954

Gnomad4 OTH exome AF: 0.0966

GnomAD4 genome AF: 0.119 AC: 18114 AN: 152094 Hom.: 1236 Cov.: 32 AF XY: 0.119 AC XY: 8836 AN XY: 74344

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.0775

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.0835

Gnomad4 FIN AF: 0.0839

Gnomad4 NFE AF: 0.0929

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0959 Hom.: 218

Bravo AF: 0.125

Asia WGS AF: 0.111 AC: 384 AN: 3478

EpiCase AF: 0.0897

EpiControl AF: 0.0870

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	9.5
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11563071; hg19: chr2-234915540; COSMIC: COSV61222196;