rs6431648

Variant names:

• chr2-233924812-G-A
• rs6431648
• NM_024080.5:c.-5-1721G>A

Variant summary

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

The NM_024080.5(TRPM8):​c.-5-1721G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 152,200 control chromosomes in the GnomAD database, including 18,470 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 0.41 (18470 hom., cov: 33)
• Consequence: TRPM8 NM_024080.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.560
• Publications: 2 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=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024080.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM8	NM_024080.5	MANE Select	c.-5-1721G>A		intron	N/A	NP_076985.4
	TRPM8	NM_001397606.1		c.-5-1721G>A		intron	N/A	NP_001384535.1
	TRPM8	NM_001397608.1		c.-5-1721G>A		intron	N/A	NP_001384537.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM8	ENST00000324695.9	TSL:1 MANE Select	c.-5-1721G>A		intron	N/A	ENSP00000323926.4
	TRPM8	ENST00000444298.5	TSL:1	n.-5-1721G>A		intron	N/A	ENSP00000396745.1
	TRPM8	ENST00000433712.6	TSL:5	c.-728-1721G>A		intron	N/A	ENSP00000404423.3

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62866 AN: 152082 Hom.: 18416 Cov.: 33

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.414 AC: 62994 AN: 152200 Hom.: 18470 Cov.: 33 AF XY: 0.415 AC XY: 30876 AN XY: 74408

African (AFR) AF: 0.806 AC: 33458 AN: 41514

American (AMR) AF: 0.408 AC: 6238 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 543 AN: 3464

East Asian (EAS) AF: 0.661 AC: 3429 AN: 5188

South Asian (SAS) AF: 0.450 AC: 2168 AN: 4816

European-Finnish (FIN) AF: 0.176 AC: 1870 AN: 10600

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14150 AN: 67998

Other (OTH) AF: 0.365 AC: 772 AN: 2114

Alfa AF: 0.276 Hom.: 25497

Bravo AF: 0.445

Asia WGS AF: 0.611 AC: 2125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.3
DANN	Benign	0.70
PhyloP100		-0.56
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: rs6431648; hg19: chr2-234833457; COSMIC: COSV61222820; COSMIC: COSV61222820;