rs2362295

Variant names:

• chr2-233997882-C-T
• rs2362295
• NM_024080.5:c.3130+1366C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024080.5(TRPM8):​c.3130+1366C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 152,024 control chromosomes in the GnomAD database, including 47,100 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 0.79 (47100 hom., cov: 30)
• Consequence: TRPM8 NM_024080.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM8	NM_024080.5	c.3130+1366C>T		intron_variant	Intron 22 of 25	ENST00000324695.9	NP_076985.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM8	ENST00000324695.9	c.3130+1366C>T		intron_variant	Intron 22 of 25	1	NM_024080.5	ENSP00000323926.4

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119322 AN: 151906 Hom.: 47062 Cov.: 30

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.804

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.794

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

GnomAD4 genome AF: 0.785 AC: 119413 AN: 152024 Hom.: 47100 Cov.: 30 AF XY: 0.783 AC XY: 58200 AN XY: 74324

African (AFR) AF: 0.852 AC: 35332 AN: 41466

American (AMR) AF: 0.757 AC: 11572 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.804 AC: 2793 AN: 3472

East Asian (EAS) AF: 0.775 AC: 3999 AN: 5158

South Asian (SAS) AF: 0.680 AC: 3269 AN: 4808

European-Finnish (FIN) AF: 0.768 AC: 8105 AN: 10556

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.760 AC: 51666 AN: 67964

Other (OTH) AF: 0.790 AC: 1669 AN: 2112

Alfa AF: 0.765 Hom.: 95597

Bravo AF: 0.790

Asia WGS AF: 0.730 AC: 2536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.62
DANN	Benign	0.16
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs2362295; hg19: chr2-234906526;