rs1003540

Variant names:

• chr2-233917239-A-G
• rs1003540
• NM_024080.5:c.-199A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024080.5(TRPM8):​c.-199A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 152,142 control chromosomes in the GnomAD database, including 17,708 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 0.40 (17708 hom., cov: 32)
• Consequence: TRPM8 NM_024080.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.431

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM8	NM_024080.5	c.-199A>G		upstream_gene_variant		ENST00000324695.9	NP_076985.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM8	ENST00000324695.9	c.-199A>G		upstream_gene_variant		1	NM_024080.5	ENSP00000323926.4
TRPM8	ENST00000444298.5	n.-199A>G		upstream_gene_variant		1		ENSP00000396745.1
TRPM8	ENST00000433712.6	c.-922A>G		upstream_gene_variant		5		ENSP00000404423.3

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60676 AN: 152022 Hom.: 17659 Cov.: 32

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.400 AC: 60791 AN: 152142 Hom.: 17708 Cov.: 32 AF XY: 0.399 AC XY: 29725 AN XY: 74406

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.645

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.347

Alfa AF: 0.232 Hom.: 5514

Bravo AF: 0.428

Asia WGS AF: 0.600 AC: 2087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.61

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1003540; hg19: chr2-234825884;