chr2-233951462-C-T

Variant names:

• chr2-233951462-C-T
• rs6740118
• NM_024080.5:c.1140+1316C>T

Variant summary

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

The NM_024080.5(TRPM8):​c.1140+1316C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,018 control chromosomes in the GnomAD database, including 16,989 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 0.38 (16989 hom., cov: 32)
• Consequence: TRPM8 NM_024080.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255
• 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]

ENSG00000237581 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.788 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM8	NM_024080.5	MANE Select	c.1140+1316C>T		intron	N/A	NP_076985.4
	TRPM8	NM_001397606.1		c.1140+1316C>T		intron	N/A	NP_001384535.1
	TRPM8	NM_001397607.1		c.990+1316C>T		intron	N/A	NP_001384536.1	A0A1L1Z857

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM8	ENST00000324695.9	TSL:1 MANE Select	c.1140+1316C>T		intron	N/A	ENSP00000323926.4	Q7Z2W7-1
	TRPM8	ENST00000444298.5	TSL:1	n.*419+1316C>T		intron	N/A	ENSP00000396745.1	F8WD55
	TRPM8	ENST00000433712.7	TSL:5	c.1140+1316C>T		intron	N/A	ENSP00000404423.4

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57066 AN: 151900 Hom.: 16931 Cov.: 32

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.376 AC: 57198 AN: 152018 Hom.: 16989 Cov.: 32 AF XY: 0.378 AC XY: 28077 AN XY: 74262

African (AFR) AF: 0.795 AC: 32993 AN: 41478

American (AMR) AF: 0.366 AC: 5586 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 376 AN: 3468

East Asian (EAS) AF: 0.670 AC: 3439 AN: 5132

South Asian (SAS) AF: 0.432 AC: 2079 AN: 4810

European-Finnish (FIN) AF: 0.148 AC: 1565 AN: 10566

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10351 AN: 67980

Other (OTH) AF: 0.316 AC: 665 AN: 2104

Alfa AF: 0.323 Hom.: 2917

Bravo AF: 0.405

Asia WGS AF: 0.597 AC: 2077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.83
PhyloP100		-0.26
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: rs6740118; hg19: chr2-234860106;