chr2-234015310-C-T

Variant names:

• chr2-234015310-C-T
• rs11563201
• NM_024080.5:c.*42+656C>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.*42+656C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 151,102 control chromosomes in the GnomAD database, including 1,945 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 (1945 hom., cov: 32)
• Consequence: TRPM8 NM_024080.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.01
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.217 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM8	NM_024080.5	MANE Select	c.*42+656C>T		intron	N/A	NP_076985.4
	TRPM8	NM_001397607.1		c.*42+656C>T		intron	N/A	NP_001384536.1
	TRPM8	NM_001397609.1		c.*42+656C>T		intron	N/A	NP_001384538.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM8	ENST00000324695.9	TSL:1 MANE Select	c.*42+656C>T		intron	N/A	ENSP00000323926.4
	TRPM8	ENST00000439148.1	TSL:1	n.*583+656C>T		intron	N/A	ENSP00000390609.1
	TRPM8	ENST00000444298.5	TSL:1	n.*2306+656C>T		intron	N/A	ENSP00000396745.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22782 AN: 151018 Hom.: 1938 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.0244

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.151 AC: 22795 AN: 151102 Hom.: 1945 Cov.: 32 AF XY: 0.152 AC XY: 11227 AN XY: 73768

African (AFR) AF: 0.119 AC: 4906 AN: 41148

American (AMR) AF: 0.224 AC: 3404 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 944 AN: 3466

East Asian (EAS) AF: 0.0246 AC: 127 AN: 5158

South Asian (SAS) AF: 0.0993 AC: 476 AN: 4792

European-Finnish (FIN) AF: 0.153 AC: 1552 AN: 10152

Middle Eastern (MID) AF: 0.161 AC: 47 AN: 292

European-Non Finnish (NFE) AF: 0.159 AC: 10769 AN: 67874

Other (OTH) AF: 0.159 AC: 332 AN: 2084

Alfa AF: 0.158 Hom.: 329

Bravo AF: 0.154

Asia WGS AF: 0.0670 AC: 235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.010
DANN	Benign	0.54
PhyloP100		-5.0
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: rs11563201; hg19: chr2-234923954;