rs11563071

Variant names:

• chr2-234006896-C-G
• rs11563071
• NM_024080.5:c.3174C>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_024080.5(TRPM8):​c.3174C>G​(p.Val1058Val) 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 NM_024080.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TRPM8	NM_024080.5	c.3174C>G	p.Val1058Val	synonymous_variant	Exon 23 of 26	ENST00000324695.9	NP_076985.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM8	ENST00000324695.9	c.3174C>G	p.Val1058Val	synonymous_variant	Exon 23 of 26	1	NM_024080.5	ENSP00000323926.4

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

GnomAD2 exomes AF: 0.104 AC: 26096 AN: 251164 AF XY: 0.0993

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 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

African (AFR) AF: 0.181 AC: 6049 AN: 33426

American (AMR) AF: 0.143 AC: 6389 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.0765 AC: 1998 AN: 26126

East Asian (EAS) AF: 0.105 AC: 4172 AN: 39678

South Asian (SAS) AF: 0.0837 AC: 7209 AN: 86136

European-Finnish (FIN) AF: 0.0838 AC: 4472 AN: 53382

Middle Eastern (MID) AF: 0.0984 AC: 567 AN: 5764

European-Non Finnish (NFE) AF: 0.0954 AC: 105928 AN: 1110258

Other (OTH) AF: 0.0966 AC: 5825 AN: 60316

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

African (AFR) AF: 0.181 AC: 7497 AN: 41456

American (AMR) AF: 0.119 AC: 1813 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0775 AC: 269 AN: 3472

East Asian (EAS) AF: 0.115 AC: 596 AN: 5180

South Asian (SAS) AF: 0.0835 AC: 401 AN: 4800

European-Finnish (FIN) AF: 0.0839 AC: 889 AN: 10600

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0929 AC: 6316 AN: 67988

Other (OTH) AF: 0.114 AC: 241 AN: 2110

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
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11563071; hg19: chr2-234915540; COSMIC: COSV61222196;