rs6741751

Positions:

• chr2-233919016-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024080.5(TRPM8):​c.-6+1584G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0777 in 151,780 control chromosomes in the GnomAD database, including 583 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 0.078 (583 hom., cov: 31)
• Consequence: TRPM8 NM_024080.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPM8	NM_024080.5	c.-6+1584G>A		intron_variant		ENST00000324695.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM8	ENST00000324695.9	c.-6+1584G>A		intron_variant		1	NM_024080.5	P1
TRPM8	ENST00000444298.5	c.-6+1584G>A		intron_variant, NMD_transcript_variant		1
TRPM8	ENST00000433712.6	c.-729+1584G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0778 AC: 11803 AN: 151664 Hom.: 584 Cov.: 31

Gnomad AFR AF: 0.0374

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.0680

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.0500

Gnomad SAS AF: 0.0545

Gnomad FIN AF: 0.0586

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0872

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

GnomAD4 genome AF: 0.0777 AC: 11798 AN: 151780 Hom.: 583 Cov.: 31 AF XY: 0.0756 AC XY: 5610 AN XY: 74190

Gnomad4 AFR AF: 0.0373

Gnomad4 AMR AF: 0.0677

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.0500

Gnomad4 SAS AF: 0.0550

Gnomad4 FIN AF: 0.0586

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.0863

Alfa AF: 0.0856 Hom.: 80

Bravo AF: 0.0794

Asia WGS AF: 0.0520 AC: 183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.63

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: rs6741751; hg19: chr2-234827661;