rs2278133

Variant names:

• chr15-31061185-A-G
• rs2278133
• NM_001252024.2:c.1162+257T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-31061185-A-G
• chr15-31061185-A-C
• chr15-31061185-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001252024.2(TRPM1):​c.1162+257T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 152,186 control chromosomes in the GnomAD database, including 26,136 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.55 (26136 hom., cov: 32)
• Consequence: TRPM1 NM_001252024.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.492
• Publications: 3 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: Labcorp Genetics (formerly Invitae), G2P
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 15-31061185-A-G is Benign according to our data. Variant chr15-31061185-A-G is described in ClinVar as Benign. ClinVar VariationId is 1295685.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001252024.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM1	NM_001252024.2	MANE Select	c.1162+257T>C		intron	N/A	NP_001238953.1	Q7Z4N2-6
	TRPM1	NM_001252020.2		c.1213+257T>C		intron	N/A	NP_001238949.1	Q7Z4N2-5
	TRPM1	NM_002420.6		c.1096+257T>C		intron	N/A	NP_002411.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM1	ENST00000256552.11	TSL:1 MANE Select	c.1162+257T>C		intron	N/A	ENSP00000256552.7	Q7Z4N2-6
	TRPM1	ENST00000558445.6	TSL:1	c.1213+257T>C		intron	N/A	ENSP00000452946.2	Q7Z4N2-5
	TRPM1	ENST00000397795.7	TSL:1	c.1096+257T>C		intron	N/A	ENSP00000380897.2	Q7Z4N2-1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 84055 AN: 152068 Hom.: 26131 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.731

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.584

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

GnomAD4 genome AF: 0.553 AC: 84089 AN: 152186 Hom.: 26136 Cov.: 32 AF XY: 0.560 AC XY: 41682 AN XY: 74414

African (AFR) AF: 0.242 AC: 10069 AN: 41524

American (AMR) AF: 0.637 AC: 9736 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 2272 AN: 3470

East Asian (EAS) AF: 0.942 AC: 4882 AN: 5184

South Asian (SAS) AF: 0.577 AC: 2786 AN: 4828

European-Finnish (FIN) AF: 0.731 AC: 7739 AN: 10580

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44750 AN: 67986

Other (OTH) AF: 0.585 AC: 1236 AN: 2114

Alfa AF: 0.626 Hom.: 51136

Bravo AF: 0.533

Asia WGS AF: 0.695 AC: 2416 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.5
DANN	Benign	0.55
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

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: rs2278133; hg19: chr15-31353388;