15-31101879-C-T

Variant names:

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

Variant summary

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

The NM_001252020.2(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 NM_001252020.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.635

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM1	NM_001252020.2	c.55-24895G>A		intron_variant	Intron 1 of 26		NP_001238949.1
TRPM1	NM_001252024.2	c.-306G>A		upstream_gene_variant		ENST00000256552.11	NP_001238953.1
TRPM1	NM_002420.6	c.-286G>A		upstream_gene_variant			NP_002411.3
TRPM1	NM_001252030.2	c.-286G>A		upstream_gene_variant			NP_001238959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM1	ENST00000256552.11	c.-306G>A		upstream_gene_variant		1	NM_001252024.2	ENSP00000256552.7

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

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.234

Alfa AF: 0.231 Hom.: 794

Bravo AF: 0.251

Asia WGS AF: 0.266 AC: 925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.8
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11070811; hg19: chr15-31394082;