chr2-233991869-G-A

Variant names:

• chr2-233991869-G-A
• rs2362294
• NM_024080.5:c.2940-4457G>A

Variant summary

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

The NM_024080.5(TRPM8):​c.2940-4457G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,922 control chromosomes in the GnomAD database, including 13,847 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 0.42 (13847 hom., cov: 32)
• Consequence: TRPM8 NM_024080.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 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.2940-4457G>A		intron	N/A	NP_076985.4
	TRPM8	NM_001397606.1		c.2940-4457G>A		intron	N/A	NP_001384535.1
	TRPM8	NM_001397607.1		c.2790-4457G>A		intron	N/A	NP_001384536.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM8	ENST00000324695.9	TSL:1 MANE Select	c.2940-4457G>A		intron	N/A	ENSP00000323926.4
	TRPM8	ENST00000439148.1	TSL:1	n.*166-4457G>A		intron	N/A	ENSP00000390609.1
	TRPM8	ENST00000444298.5	TSL:1	n.*1889-4457G>A		intron	N/A	ENSP00000396745.1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64391 AN: 151804 Hom.: 13824 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.424 AC: 64471 AN: 151922 Hom.: 13847 Cov.: 32 AF XY: 0.425 AC XY: 31526 AN XY: 74238

African (AFR) AF: 0.418 AC: 17300 AN: 41426

American (AMR) AF: 0.481 AC: 7348 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1441 AN: 3472

East Asian (EAS) AF: 0.522 AC: 2700 AN: 5174

South Asian (SAS) AF: 0.498 AC: 2395 AN: 4814

European-Finnish (FIN) AF: 0.345 AC: 3626 AN: 10504

Middle Eastern (MID) AF: 0.404 AC: 118 AN: 292

European-Non Finnish (NFE) AF: 0.414 AC: 28143 AN: 67942

Other (OTH) AF: 0.418 AC: 882 AN: 2108

Alfa AF: 0.423 Hom.: 36940

Bravo AF: 0.436

Asia WGS AF: 0.518 AC: 1800 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.40
PhyloP100		0.036
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: rs2362294; hg19: chr2-234900513;