NM_024080.5:c.118-366G>C

Variant names:

• chr2-233930302-G-C
• rs10803666
• NM_024080.5:c.118-366G>C

Variant summary

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

The NM_024080.5(TRPM8):​c.118-366G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,164 control chromosomes in the GnomAD database, including 1,043 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 0.11 (1043 hom., cov: 32)
• Consequence: TRPM8 NM_024080.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.749
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM8	NM_024080.5	c.118-366G>C		intron_variant	Intron 2 of 25	ENST00000324695.9	NP_076985.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM8	ENST00000324695.9	c.118-366G>C		intron_variant	Intron 2 of 25	1	NM_024080.5	ENSP00000323926.4

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16702 AN: 152046 Hom.: 1038 Cov.: 32

Gnomad AFR AF: 0.0985

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.0880

Gnomad FIN AF: 0.0503

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.110 AC: 16720 AN: 152164 Hom.: 1043 Cov.: 32 AF XY: 0.110 AC XY: 8172 AN XY: 74386

African (AFR) AF: 0.0985 AC: 4087 AN: 41492

American (AMR) AF: 0.157 AC: 2401 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 352 AN: 3468

East Asian (EAS) AF: 0.219 AC: 1132 AN: 5172

South Asian (SAS) AF: 0.0883 AC: 425 AN: 4814

European-Finnish (FIN) AF: 0.0503 AC: 533 AN: 10588

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7276 AN: 68018

Other (OTH) AF: 0.121 AC: 256 AN: 2112

Alfa AF: 0.101 Hom.: 92

Bravo AF: 0.120

Asia WGS AF: 0.164 AC: 570 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.38
DANN	Benign	0.77
PhyloP100		-0.75
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: rs10803666; hg19: chr2-234838947;