rs11563201

Positions:

• chr2-234015310-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024080.5(TRPM8):​c.*42+656C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 151,102 control chromosomes in the GnomAD database, including 1,945 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 0.15 (1945 hom., cov: 32)
• Consequence: TRPM8 NM_024080.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.01

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM8	NM_024080.5	c.*42+656C>T		intron_variant		ENST00000324695.9	NP_076985.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM8	ENST00000324695.9	c.*42+656C>T		intron_variant		1	NM_024080.5	ENSP00000323926	P1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22782 AN: 151018 Hom.: 1938 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.0244

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.151 AC: 22795 AN: 151102 Hom.: 1945 Cov.: 32 AF XY: 0.152 AC XY: 11227 AN XY: 73768

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.0246

Gnomad4 SAS AF: 0.0993

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.159

Alfa AF: 0.158 Hom.: 329

Bravo AF: 0.154

Asia WGS AF: 0.0670 AC: 235 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	0.010
DANN	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs11563201; hg19: chr2-234923954;