rs28441327

Variant names:

• chr15-31103143-C-T
• rs28441327
• ENST00000558445.6:c.55-26159G>A

Variant summary

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

The ENST00000558445.6(TRPM1):​c.55-26159G>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 ENST00000558445.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.251
• Publications: 1 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=-0.97).
• 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 rank	MANE	Protein	UniProt
TRPM1	NM_001252020.2	c.55-26159G>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.55-26159G>A		intron_variant	Intron 1 of 26	1		ENSP00000452946.2
TRPM1	ENST00000559177.6	c.55-26159G>A		intron_variant	Intron 1 of 7	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

African (AFR) AF: 0.344 AC: 14252 AN: 41488

American (AMR) AF: 0.302 AC: 4621 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 532 AN: 3470

East Asian (EAS) AF: 0.164 AC: 848 AN: 5176

South Asian (SAS) AF: 0.316 AC: 1524 AN: 4826

European-Finnish (FIN) AF: 0.119 AC: 1265 AN: 10602

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

European-Non Finnish (NFE) AF: 0.190 AC: 12944 AN: 67972

Other (OTH) AF: 0.238 AC: 501 AN: 2106

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
PhyloP100		-0.25
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: rs28441327; hg19: chr15-31395346;