rs28441327

Positions:

• chr15-31103143-C-T

Variant summary

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

The NM_001252020.2(TRPM1):​c.55-26159G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,134 control chromosomes in the GnomAD database, including 4,993 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 (4993 hom., cov: 33)
• Consequence: TRPM1 NM_001252020.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.251

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM1	NM_001252020.2	c.55-26159G>A		intron_variant			NP_001238949.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM1	ENST00000558445.6	c.55-26159G>A		intron_variant		1		ENSP00000452946.2
TRPM1	ENST00000559177.6	c.55-26159G>A		intron_variant		5		ENSP00000453477.2

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36670 AN: 152016 Hom.: 4974 Cov.: 33

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.242 AC: 36747 AN: 152134 Hom.: 4993 Cov.: 33 AF XY: 0.241 AC XY: 17897 AN XY: 74400

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.238

Alfa AF: 0.222 Hom.: 528

Bravo AF: 0.254

Asia WGS AF: 0.269 AC: 936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.2
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs28441327; hg19: chr15-31395346;