rs11638121

chr15-31132799-C-T

Variant summary

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

The ENST00000558445.6(TRPM1):c.54+28107G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,088 control chromosomes in the GnomAD database, including 1,877 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 0.15 (1877 hom., cov: 32)
• Consequence: TRPM1 ENST00000558445.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPM1	NM_001252020.2	c.54+28107G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM1	ENST00000558445.6	c.54+28107G>A		intron_variant		1		A2
TRPM1	ENST00000559177.6	c.54+28107G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23130 AN: 151970 Hom.: 1881 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.00348

Gnomad SAS AF: 0.0749

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.152 AC: 23120 AN: 152088 Hom.: 1877 Cov.: 32 AF XY: 0.149 AC XY: 11076 AN XY: 74336

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.00349

Gnomad4 SAS AF: 0.0750

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.165

Alfa AF: 0.156 Hom.: 207

Bravo AF: 0.150

Asia WGS AF: 0.0530 AC: 183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	5.1
Dann	Benign	0.28

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11638121; hg19: chr15-31425002;