rs12472151

chr2-233944048-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.699+1300G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0425 in 152,036 control chromosomes in the GnomAD database, including 173 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 0.042 (173 hom., cov: 32)
• Consequence: TRPM8 NM_024080.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.436

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPM8	NM_024080.5	c.699+1300G>A		intron_variant		ENST00000324695.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM8	ENST00000324695.9	c.699+1300G>A		intron_variant		1	NM_024080.5	P1
TRPM8	ENST00000444298.5	c.699+1300G>A		intron_variant, NMD_transcript_variant		1
TRPM8	ENST00000433712.6	c.-25+1300G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0424 AC: 6439 AN: 151916 Hom.: 168 Cov.: 32

Gnomad AFR AF: 0.0261

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0740

Gnomad ASJ AF: 0.0485

Gnomad EAS AF: 0.0712

Gnomad SAS AF: 0.0405

Gnomad FIN AF: 0.0198

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0462

Gnomad OTH AF: 0.0569

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

GnomAD4 genome AF: 0.0425 AC: 6454 AN: 152036 Hom.: 173 Cov.: 32 AF XY: 0.0421 AC XY: 3128 AN XY: 74278

Gnomad4 AFR AF: 0.0261

Gnomad4 AMR AF: 0.0748

Gnomad4 ASJ AF: 0.0485

Gnomad4 EAS AF: 0.0712

Gnomad4 SAS AF: 0.0405

Gnomad4 FIN AF: 0.0198

Gnomad4 NFE AF: 0.0462

Gnomad4 OTH AF: 0.0563

Alfa AF: 0.0451 Hom.: 62

Bravo AF: 0.0475

Asia WGS AF: 0.0490 AC: 172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.56
Dann	Benign	0.36

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: rs12472151; hg19: chr2-234852692;