rs2052029

chr2-234019044-C-Gchr2-234019044-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.*1788C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 151,876 control chromosomes in the GnomAD database, including 42,692 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 0.75 (42692 hom., cov: 30)
  • Failed GnomAD Quality Control
• Consequence: TRPM8 NM_024080.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.791

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPM8	NM_024080.5	c.*1788C>G		3_prime_UTR_variant	26/26	ENST00000324695.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM8	ENST00000324695.9	c.*1788C>G		3_prime_UTR_variant	26/26	1	NM_024080.5	P1
TRPM8	ENST00000433712.6	c.*1788C>G		3_prime_UTR_variant	24/24	5

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113127 AN: 151758 Hom.: 42637 Cov.: 30

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.739

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.750

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.746 AC: 113241 AN: 151876 Hom.: 42692 Cov.: 30 AF XY: 0.748 AC XY: 55508 AN XY: 74230

Gnomad4 AFR AF: 0.847

Gnomad4 AMR AF: 0.804

Gnomad4 ASJ AF: 0.692

Gnomad4 EAS AF: 0.811

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.699

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.750

Alfa AF: 0.618 Hom.: 1683

Bravo AF: 0.758

Asia WGS AF: 0.735 AC: 2555 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.62
Dann	Benign	0.66

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: rs2052029; hg19: chr2-234927688;