chr2-233944048-G-A

Variant names:

• chr2-233944048-G-A
• rs12472151
• NM_024080.5:c.699+1300G>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.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
• Publications: 9 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 (AMR) allele frequency at 95% confidence interval = 0.0712 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.699+1300G>A		intron	N/A	NP_076985.4
	TRPM8	NM_001397606.1		c.699+1300G>A		intron	N/A	NP_001384535.1
	TRPM8	NM_001397607.1		c.549+1300G>A		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.699+1300G>A		intron	N/A	ENSP00000323926.4	Q7Z2W7-1
	TRPM8	ENST00000444298.5	TSL:1	n.699+1300G>A		intron	N/A	ENSP00000396745.1	F8WD55
	TRPM8	ENST00000433712.7	TSL:5	c.699+1300G>A		intron	N/A	ENSP00000404423.4

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

African (AFR) AF: 0.0261 AC: 1082 AN: 41496

American (AMR) AF: 0.0748 AC: 1142 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0485 AC: 168 AN: 3462

East Asian (EAS) AF: 0.0712 AC: 368 AN: 5170

South Asian (SAS) AF: 0.0405 AC: 195 AN: 4812

European-Finnish (FIN) AF: 0.0198 AC: 209 AN: 10562

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0462 AC: 3137 AN: 67948

Other (OTH) AF: 0.0563 AC: 119 AN: 2112

Alfa AF: 0.0448 Hom.: 74

Bravo AF: 0.0475

Asia WGS AF: 0.0490 AC: 172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.56
DANN	Benign	0.36
PhyloP100		-0.44
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: rs12472151; hg19: chr2-234852692;