rs17862920

Variant names:

• chr2-233919350-C-T
• rs17862920
• NM_024080.5:c.-6+1918C>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.-6+1918C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,060 control chromosomes in the GnomAD database, including 986 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 0.10 (986 hom., cov: 31)
• Consequence: TRPM8 NM_024080.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.421
• Publications: 14 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM8	NM_024080.5	c.-6+1918C>T		intron_variant	Intron 1 of 25	ENST00000324695.9	NP_076985.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM8	ENST00000324695.9	c.-6+1918C>T		intron_variant	Intron 1 of 25	1	NM_024080.5	ENSP00000323926.4
TRPM8	ENST00000444298.5	n.-6+1918C>T		intron_variant	Intron 1 of 24	1		ENSP00000396745.1
TRPM8	ENST00000433712.6	c.-729+1918C>T		intron_variant	Intron 1 of 23	5		ENSP00000404423.3

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15268 AN: 151942 Hom.: 987 Cov.: 31

Gnomad AFR AF: 0.0686

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.0732

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.0586

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.100 AC: 15269 AN: 152060 Hom.: 986 Cov.: 31 AF XY: 0.101 AC XY: 7531 AN XY: 74328

African (AFR) AF: 0.0686 AC: 2849 AN: 41504

American (AMR) AF: 0.0730 AC: 1115 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 399 AN: 3464

East Asian (EAS) AF: 0.274 AC: 1408 AN: 5134

South Asian (SAS) AF: 0.221 AC: 1061 AN: 4810

European-Finnish (FIN) AF: 0.0586 AC: 620 AN: 10578

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7342 AN: 67982

Other (OTH) AF: 0.101 AC: 212 AN: 2108

Alfa AF: 0.107 Hom.: 603

Bravo AF: 0.0997

Asia WGS AF: 0.230 AC: 799 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.64
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17862920; hg19: chr2-234827995;