15-31049313-C-T

Variant names:

• chr15-31049313-C-T
• rs2288241
• NM_001252024.2:c.1572+62G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001252024.2(TRPM1):​c.1572+62G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 1,610,592 control chromosomes in the GnomAD database, including 242,158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (18747 hom., cov: 32)
  • Exomes 𝑓: 0.55 (223411 hom.)
• Consequence: TRPM1 NM_001252024.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.252
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-31049313-C-T is Benign according to our data. Variant chr15-31049313-C-T is described in CliVar as Benign. Clinvar id is 1261772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-31049313-C-T is described in CliVar as Benign. Clinvar id is 1261772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-31049313-C-T is described in CliVar as Benign. Clinvar id is 1261772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-31049313-C-T is described in CliVar as Benign. Clinvar id is 1261772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-31049313-C-T is described in CliVar as Benign. Clinvar id is 1261772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-31049313-C-T is described in CliVar as Benign. Clinvar id is 1261772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-31049313-C-T is described in CliVar as Benign. Clinvar id is 1261772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-31049313-C-T is described in CliVar as Benign. Clinvar id is 1261772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-31049313-C-T is described in CliVar as Benign. Clinvar id is 1261772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM1	NM_001252024.2	c.1572+62G>A		intron_variant	Intron 13 of 27	ENST00000256552.11	NP_001238953.1
TRPM1	NM_001252020.2	c.1623+62G>A		intron_variant	Intron 12 of 26		NP_001238949.1
TRPM1	NM_002420.6	c.1506+62G>A		intron_variant	Intron 12 of 26		NP_002411.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM1	ENST00000256552.11	c.1572+62G>A		intron_variant	Intron 13 of 27	1	NM_001252024.2	ENSP00000256552.7

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70884 AN: 151968 Hom.: 18751 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.940

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.497

GnomAD4 exome AF: 0.546 AC: 797028 AN: 1458504 Hom.: 223411 AF XY: 0.545 AC XY: 395415 AN XY: 725712

African (AFR) AF: 0.187 AC: 6266 AN: 33426

American (AMR) AF: 0.589 AC: 26336 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 14382 AN: 26102

East Asian (EAS) AF: 0.909 AC: 36066 AN: 39678

South Asian (SAS) AF: 0.476 AC: 40967 AN: 86086

European-Finnish (FIN) AF: 0.536 AC: 28194 AN: 52604

Middle Eastern (MID) AF: 0.459 AC: 2636 AN: 5740

European-Non Finnish (NFE) AF: 0.549 AC: 609358 AN: 1109912

Other (OTH) AF: 0.545 AC: 32823 AN: 60256

GnomAD4 genome AF: 0.466 AC: 70901 AN: 152088 Hom.: 18747 Cov.: 32 AF XY: 0.470 AC XY: 34957 AN XY: 74346

African (AFR) AF: 0.207 AC: 8579 AN: 41484

American (AMR) AF: 0.565 AC: 8633 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1921 AN: 3466

East Asian (EAS) AF: 0.940 AC: 4867 AN: 5180

South Asian (SAS) AF: 0.505 AC: 2434 AN: 4820

European-Finnish (FIN) AF: 0.539 AC: 5696 AN: 10574

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37204 AN: 67962

Other (OTH) AF: 0.497 AC: 1050 AN: 2114

Alfa AF: 0.451 Hom.: 2592

Bravo AF: 0.458

Asia WGS AF: 0.649 AC: 2252 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.34
DANN	Benign	0.53
PhyloP100		-0.25
Mutation Taster		=20/80	disease causing (long InDel)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2288241; hg19: chr15-31341516; COSMIC: COSV56632205;