rs1016062

Variant names:

• chr2-233986249-G-A
• rs1016062
• NM_024080.5:c.2939+384G>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.2939+384G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,098 control chromosomes in the GnomAD database, including 2,034 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 0.15 (2034 hom., cov: 33)
• Consequence: TRPM8 NM_024080.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.809
• 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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.402 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.2939+384G>A		intron	N/A	NP_076985.4
	TRPM8	NM_001397606.1		c.2939+384G>A		intron	N/A	NP_001384535.1
	TRPM8	NM_001397607.1		c.2789+384G>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.2939+384G>A		intron	N/A	ENSP00000323926.4	Q7Z2W7-1
	TRPM8	ENST00000439148.1	TSL:1	n.*165+384G>A		intron	N/A	ENSP00000390609.1	H7BZP4
	TRPM8	ENST00000444298.5	TSL:1	n.*1888+384G>A		intron	N/A	ENSP00000396745.1	F8WD55

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23561 AN: 151980 Hom.: 2029 Cov.: 33

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.155 AC: 23570 AN: 152098 Hom.: 2034 Cov.: 33 AF XY: 0.159 AC XY: 11855 AN XY: 74330

African (AFR) AF: 0.129 AC: 5367 AN: 41496

American (AMR) AF: 0.150 AC: 2289 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 607 AN: 3472

East Asian (EAS) AF: 0.416 AC: 2150 AN: 5164

South Asian (SAS) AF: 0.168 AC: 809 AN: 4814

European-Finnish (FIN) AF: 0.201 AC: 2119 AN: 10544

Middle Eastern (MID) AF: 0.120 AC: 35 AN: 292

European-Non Finnish (NFE) AF: 0.144 AC: 9819 AN: 68004

Other (OTH) AF: 0.156 AC: 329 AN: 2112

Alfa AF: 0.151 Hom.: 3524

Bravo AF: 0.153

Asia WGS AF: 0.245 AC: 850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.3
DANN	Benign	0.81
PhyloP100		0.81
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: rs1016062; hg19: chr2-234894893;