rs7182946

Variant names:

• chr15-31102665-G-T
• rs7182946
• ENST00000558445.6:c.55-25681C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000558445.6(TRPM1):​c.55-25681C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 152,072 control chromosomes in the GnomAD database, including 28,833 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 0.61 (28833 hom., cov: 33)
• Consequence: TRPM1 ENST00000558445.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.612
• Publications: 8 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM1	NM_001252020.2	c.55-25681C>A		intron_variant	Intron 1 of 26		NP_001238949.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM1	ENST00000558445.6	c.55-25681C>A		intron_variant	Intron 1 of 26	1		ENSP00000452946.2
TRPM1	ENST00000559177.6	c.55-25681C>A		intron_variant	Intron 1 of 7	5		ENSP00000453477.2

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92659 AN: 151954 Hom.: 28800 Cov.: 33

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.960

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.630

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

GnomAD4 genome AF: 0.610 AC: 92747 AN: 152072 Hom.: 28833 Cov.: 33 AF XY: 0.614 AC XY: 45627 AN XY: 74324

African (AFR) AF: 0.615 AC: 25502 AN: 41488

American (AMR) AF: 0.706 AC: 10789 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1864 AN: 3466

East Asian (EAS) AF: 0.960 AC: 4955 AN: 5160

South Asian (SAS) AF: 0.680 AC: 3275 AN: 4816

European-Finnish (FIN) AF: 0.543 AC: 5737 AN: 10562

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38643 AN: 67982

Other (OTH) AF: 0.631 AC: 1333 AN: 2114

Alfa AF: 0.578 Hom.: 13155

Bravo AF: 0.622

Asia WGS AF: 0.807 AC: 2805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.48
DANN	Benign	0.82
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7182946; hg19: chr15-31394868;