rs2113945

Variant names:

• chr15-31032328-G-A
• rs2113945
• NM_001252024.2:c.2952+361C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-31032328-G-A
• chr15-31032328-G-C
• chr15-31032328-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

TRPM1 Gene-Disease associations (from GenCC):

• congenital stationary night blindness 1C

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• TRPM1-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• congenital stationary night blindness

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000259720 (HGNC:58477):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TRPM1	NM_001252024.2	c.2952+361C>T		intron_variant	Intron 22 of 27	ENST00000256552.11	NP_001238953.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM1	ENST00000256552.11	c.2952+361C>T		intron_variant	Intron 22 of 27	1	NM_001252024.2	ENSP00000256552.7

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

African (AFR) AF: 0.541 AC: 22353 AN: 41338

American (AMR) AF: 0.289 AC: 4415 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 980 AN: 3468

East Asian (EAS) AF: 0.131 AC: 675 AN: 5168

South Asian (SAS) AF: 0.198 AC: 951 AN: 4814

European-Finnish (FIN) AF: 0.123 AC: 1301 AN: 10546

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16595 AN: 67932

Other (OTH) AF: 0.324 AC: 684 AN: 2108

Alfa AF: 0.262 Hom.: 2877

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
PhyloP100		0.86
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2113945; hg19: chr15-31324531;