2-233996434-C-T

Position:

• chr2-233996434-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_024080.5(TRPM8):​c.3048C>T​(p.Ile1016Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 1,613,750 control chromosomes in the GnomAD database, including 58,153 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 0.22 (4384 hom., cov: 32)
  • Exomes 𝑓: 0.27 (53769 hom.)
• Consequence: TRPM8 NM_024080.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351

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]

TRPM8 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=-0.351 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM8	NM_024080.5	c.3048C>T	p.Ile1016Ile	synonymous_variant	22/26	ENST00000324695.9	NP_076985.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM8	ENST00000324695.9	c.3048C>T	p.Ile1016Ile	synonymous_variant	22/26	1	NM_024080.5	ENSP00000323926.4

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33737 AN: 151996 Hom.: 4375 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.0843

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.225

GnomAD3 exomes AF: 0.248 AC: 62449 AN: 251374 Hom.: 8958 AF XY: 0.244 AC XY: 33148 AN XY: 135852

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.389

Gnomad ASJ exome AF: 0.209

Gnomad EAS exome AF: 0.0845

Gnomad SAS exome AF: 0.175

Gnomad FIN exome AF: 0.199

Gnomad NFE exome AF: 0.285

Gnomad OTH exome AF: 0.259

GnomAD4 exome AF: 0.265 AC: 387621 AN: 1461636 Hom.: 53769 Cov.: 35 AF XY: 0.263 AC XY: 191161 AN XY: 727146

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.382

Gnomad4 ASJ exome AF: 0.207

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.178

Gnomad4 FIN exome AF: 0.214

Gnomad4 NFE exome AF: 0.283

Gnomad4 OTH exome AF: 0.247

GnomAD4 genome AF: 0.222 AC: 33754 AN: 152114 Hom.: 4384 Cov.: 32 AF XY: 0.218 AC XY: 16177 AN XY: 74340

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.0839

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.221

Alfa AF: 0.264 Hom.: 9369

Bravo AF: 0.230

Asia WGS AF: 0.113 AC: 393 AN: 3478

EpiCase AF: 0.284

EpiControl AF: 0.286

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.6
DANN	Benign	0.65

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: rs11563208; hg19: chr2-234905078; COSMIC: COSV61223462;