2-233951462-C-T

Position:

• chr2-233951462-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM8	NM_024080.5	c.1140+1316C>T		intron_variant		ENST00000324695.9	NP_076985.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM8	ENST00000324695.9	c.1140+1316C>T		intron_variant		1	NM_024080.5	ENSP00000323926	P1
TRPM8	ENST00000444298.5	c.*419+1316C>T		intron_variant, NMD_transcript_variant		1		ENSP00000396745
	ENST00000455991.1	n.400+3574G>A		intron_variant, non_coding_transcript_variant		3
TRPM8	ENST00000433712.6	c.417+1316C>T		intron_variant		5		ENSP00000404423

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

Gnomad4 AFR AF: 0.795

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.316

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs6740118; hg19: chr2-234860106;