ENST00000558445.6:c.55-24895G>A

Variant names:

• chr15-31101879-C-T
• rs11070811
• ENST00000558445.6:c.55-24895G>A

Variant summary

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

The ENST00000558445.6(TRPM1):​c.55-24895G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,194 control chromosomes in the GnomAD database, including 4,885 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 0.24 (4885 hom., cov: 34)
• Consequence: TRPM1 ENST00000558445.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.635
• Publications: 6 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: Labcorp Genetics (formerly Invitae), G2P
• 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=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000558445.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM1	NM_001252020.2		c.55-24895G>A		intron	N/A	NP_001238949.1	Q7Z4N2-5
	TRPM1	NM_001252024.2	MANE Select	c.-306G>A		upstream_gene	N/A	NP_001238953.1	Q7Z4N2-6
	TRPM1	NM_002420.6		c.-286G>A		upstream_gene	N/A	NP_002411.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM1	ENST00000558445.6	TSL:1	c.55-24895G>A		intron	N/A	ENSP00000452946.2	Q7Z4N2-5
	TRPM1	ENST00000559177.6	TSL:5	c.55-24895G>A		intron	N/A	ENSP00000453477.2	H0YM61
	TRPM1	ENST00000256552.11	TSL:1 MANE Select	c.-306G>A		upstream_gene	N/A	ENSP00000256552.7	Q7Z4N2-6

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36318 AN: 152076 Hom.: 4867 Cov.: 34

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.239 AC: 36394 AN: 152194 Hom.: 4885 Cov.: 34 AF XY: 0.238 AC XY: 17733 AN XY: 74410

African (AFR) AF: 0.337 AC: 13975 AN: 41514

American (AMR) AF: 0.302 AC: 4618 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 523 AN: 3472

East Asian (EAS) AF: 0.148 AC: 768 AN: 5176

South Asian (SAS) AF: 0.318 AC: 1536 AN: 4826

European-Finnish (FIN) AF: 0.120 AC: 1271 AN: 10608

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12949 AN: 68004

Other (OTH) AF: 0.234 AC: 494 AN: 2110

Alfa AF: 0.234 Hom.: 849

Bravo AF: 0.251

Asia WGS AF: 0.266 AC: 925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.8
DANN	Benign	0.71
PhyloP100		0.64
PromoterAI		-0.033	Neutral
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: rs11070811; hg19: chr15-31394082;