Variant 15-31077055-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001252024.2(TRPM1):c.4-71G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 992,454 control chromosomes in the GnomAD database, including 114,788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 17811 hom., cov: 33)

Exomes 𝑓: 0.47 ( 96977 hom. )

Consequence

TRPM1
NM_001252024.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.60

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 15-31077055-C-T is Benign according to our data. Variant chr15-31077055-C-T is described in ClinVar as [Benign]. Clinvar id is 1233386.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
TRPM1	NM_001252024.2 linkuse as main transcript	c.4-71G>A	intron_variant	ENST00000256552.11	NP_001238953.1
TRPM1	NM_001252020.2 linkuse as main transcript	c.55-71G>A	intron_variant		NP_001238949.1
TRPM1	NM_001252030.2 linkuse as main transcript	c.-63-71G>A	intron_variant		NP_001238959.1
TRPM1	NM_002420.6 linkuse as main transcript	c.-63-71G>A	intron_variant		NP_002411.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM1	ENST00000256552.11 linkuse as main transcript	c.4-71G>A		intron_variant		1	NM_001252024.2	ENSP00000256552	P4	Q7Z4N2-6

Frequencies

GnomAD3 genomes

AF:

0.478

AC:

72648

AN:

151994

Hom.:

17802

Cov.:

show subpopulations

Gnomad AFR

AF:

0.464

Gnomad AMI

AF:

0.389

Gnomad AMR

AF:

0.467

Gnomad ASJ

AF:

0.389

Gnomad EAS

AF:

0.775

Gnomad SAS

AF:

0.431

Gnomad FIN

AF:

0.569

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.461

Gnomad OTH

AF:

0.483

GnomAD4 exome

AF:

0.472

AC:

396781

AN:

840342

Hom.:

96977

AF XY:

0.468

AC XY:

206435

AN XY:

440666

show subpopulations

Gnomad4 AFR exome

AF:

0.466

Gnomad4 AMR exome

AF:

0.472

Gnomad4 ASJ exome

AF:

0.388

Gnomad4 EAS exome

AF:

0.781

Gnomad4 SAS exome

AF:

0.409

Gnomad4 FIN exome

AF:

0.553

Gnomad4 NFE exome

AF:

0.458

Gnomad4 OTH exome

AF:

0.476

GnomAD4 genome

AF:

0.478

AC:

72691

AN:

152112

Hom.:

17811

Cov.:

AF XY:

0.482

AC XY:

35836

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.464

Gnomad4 AMR

AF:

0.466

Gnomad4 ASJ

AF:

0.389

Gnomad4 EAS

AF:

0.775

Gnomad4 SAS

AF:

0.432

Gnomad4 FIN

AF:

0.569

Gnomad4 NFE

AF:

0.461

Gnomad4 OTH

AF:

0.482

Alfa

AF:

0.461

Hom.:

2073

Bravo

AF:

0.475

Asia WGS

AF:

0.556

AC:

1932

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Nov 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.1

DANN

Benign

0.49

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over