rs2113945

Positions:

• chr15-31032328-G-A

Variant summary

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

The NM_001252024.2(TRPM1):​c.2952+361C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 151,832 control chromosomes in the GnomAD database, including 9,243 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 0.32 (9243 hom., cov: 31)
• Consequence: TRPM1 NM_001252024.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.862

Genes affected

TRPM1 (HGNC:7146): (transient receptor potential cation channel subfamily M member 1) This gene encodes a member of the transient receptor potential melastatin subfamily of transient receptor potential ion channels. The encoded protein is a calcium permeable cation channel that is expressed in melanocytes and may play a role in melanin synthesis. Specific mutations in this gene are the cause autosomal recessive complete congenital stationary night blindness-1C. The expression of this protein is inversely correlated with melanoma aggressiveness and as such it is used as a prognostic marker for melanoma metastasis. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2011]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPM1	NM_001252024.2	c.2952+361C>T		intron_variant		ENST00000256552.11
LOC105370752	XR_932055.2	n.279-3242G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM1	ENST00000256552.11	c.2952+361C>T		intron_variant		1	NM_001252024.2	P4
	ENST00000665655.1	n.219-3425G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48099 AN: 151714 Hom.: 9215 Cov.: 31

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.317 AC: 48181 AN: 151832 Hom.: 9243 Cov.: 31 AF XY: 0.307 AC XY: 22801 AN XY: 74212

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.324

Alfa AF: 0.262 Hom.: 2603

Bravo AF: 0.337

Asia WGS AF: 0.197 AC: 684 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.7
DANN	Benign	0.72

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: rs2113945; hg19: chr15-31324531;