rs10490018

chr2-234009088-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.3264+985C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 151,860 control chromosomes in the GnomAD database, including 5,727 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 0.26 (5727 hom., cov: 31)
• Consequence: TRPM8 NM_024080.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.475

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPM8	NM_024080.5	c.3264+985C>T		intron_variant		ENST00000324695.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM8	ENST00000324695.9	c.3264+985C>T		intron_variant		1	NM_024080.5	P1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39265 AN: 151742 Hom.: 5725 Cov.: 31

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.259 AC: 39267 AN: 151860 Hom.: 5727 Cov.: 31 AF XY: 0.263 AC XY: 19480 AN XY: 74202

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.281

Alfa AF: 0.303 Hom.: 14560

Bravo AF: 0.246

Asia WGS AF: 0.342 AC: 1191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.38
Dann	Benign	0.63

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: rs10490018; hg19: chr2-234917732;