rs12708421

Positions:

• chr15-31040036-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001252024.2(TRPM1):​c.2316+82G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,228,044 control chromosomes in the GnomAD database, including 34,713 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4507 hom., cov: 32)
  • Exomes 𝑓: 0.23 (30206 hom.)
• Consequence: TRPM1 NM_001252024.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.501

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 15-31040036-C-A is Benign according to our data. Variant chr15-31040036-C-A is described in ClinVar as [Benign]. Clinvar id is 1266664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM1	NM_001252024.2	c.2316+82G>T		intron_variant		ENST00000256552.11	NP_001238953.1
TRPM1	NM_001252020.2	c.2367+82G>T		intron_variant			NP_001238949.1
TRPM1	NM_002420.6	c.2250+82G>T		intron_variant			NP_002411.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM1	ENST00000256552.11	c.2316+82G>T		intron_variant		1	NM_001252024.2	ENSP00000256552	P4

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36396 AN: 152026 Hom.: 4500 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.254

GnomAD4 exome AF: 0.230 AC: 247605 AN: 1075900 Hom.: 30206 AF XY: 0.228 AC XY: 125375 AN XY: 550964

Gnomad4 AFR exome AF: 0.263

Gnomad4 AMR exome AF: 0.269

Gnomad4 ASJ exome AF: 0.234

Gnomad4 EAS exome AF: 0.0228

Gnomad4 SAS exome AF: 0.158

Gnomad4 FIN exome AF: 0.258

Gnomad4 NFE exome AF: 0.243

Gnomad4 OTH exome AF: 0.222

GnomAD4 genome AF: 0.240 AC: 36452 AN: 152144 Hom.: 4507 Cov.: 32 AF XY: 0.238 AC XY: 17734 AN XY: 74374

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.0108

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.254

Alfa AF: 0.248 Hom.: 960

Bravo AF: 0.244

Asia WGS AF: 0.0990 AC: 348 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs12708421; hg19: chr15-31332239;