rs6431648

Positions:

• chr2-233924812-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM8	NM_024080.5	c.-5-1721G>A		intron_variant		ENST00000324695.9	NP_076985.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM8	ENST00000324695.9	c.-5-1721G>A		intron_variant		1	NM_024080.5	ENSP00000323926	P1
TRPM8	ENST00000444298.5	c.-5-1721G>A		intron_variant, NMD_transcript_variant		1		ENSP00000396745
TRPM8	ENST00000433712.6	c.-728-1721G>A		intron_variant		5		ENSP00000404423

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

Gnomad4 AFR AF: 0.806

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.661

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.365

Alfa AF: 0.238 Hom.: 10613

Bravo AF: 0.445

Asia WGS AF: 0.611 AC: 2125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.3
DANN	Benign	0.70

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: rs6431648; hg19: chr2-234833457; COSMIC: COSV61222820; COSMIC: COSV61222820;