rs933151

Variant names:

• chr21-44416122-C-T
• rs933151
• NM_003307.4:c.3147-1805C>T

Variant summary

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

The NM_003307.4(TRPM2):​c.3147-1805C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 152,242 control chromosomes in the GnomAD database, including 42,987 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 0.75 (42938 hom., cov: 31)
  • Exomes 𝑓: 0.71 (49 hom.)
• Consequence: TRPM2 NM_003307.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• Publications: 6 publications found

Genes affected

TRPM2 (HGNC:12339): (transient receptor potential cation channel subfamily M member 2) The protein encoded by this gene forms a tetrameric cation channel that is permeable to calcium, sodium, and potassium and is regulated by free intracellular ADP-ribose. The encoded protein is activated by oxidative stress and confers susceptibility to cell death. Alternative splicing results in multiple transcript variants encoding distinct protein isoforms. Additional transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Feb 2016]

TRPM2-AS (HGNC:50758): (TRPM2 antisense RNA)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003307.4. 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
	TRPM2	NM_003307.4	MANE Select	c.3147-1805C>T		intron	N/A	NP_003298.2	O94759-1
	TRPM2	NM_001320350.2		c.3147-1805C>T		intron	N/A	NP_001307279.2	E9PGK7
	TRPM2	NM_001433516.1		c.3147-1805C>T		intron	N/A	NP_001420445.1	O94759-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM2	ENST00000397928.6	TSL:1 MANE Select	c.3147-1805C>T		intron	N/A	ENSP00000381023.1	O94759-1
	TRPM2	ENST00000397932.6	TSL:1	c.3147-1805C>T		intron	N/A	ENSP00000381026.2	E9PGK7
	TRPM2	ENST00000300482.9	TSL:1	c.3147-1805C>T		intron	N/A	ENSP00000300482.5	O94759-1

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114088 AN: 151930 Hom.: 42920 Cov.: 31

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.761

GnomAD4 exome AF: 0.711 AC: 138 AN: 194 Hom.: 49 Cov.: 0 AF XY: 0.688 AC XY: 106 AN XY: 154

African (AFR) AF: 0.750 AC: 3 AN: 4

American (AMR) AF: 1.00 AC: 2 AN: 2

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AF: 0.750 AC: 3 AN: 4

South Asian (SAS) AF: 0.250 AC: 1 AN: 4

European-Finnish (FIN) AF: 1.00 AC: 4 AN: 4

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.719 AC: 115 AN: 160

Other (OTH) AF: 0.583 AC: 7 AN: 12

GnomAD4 genome AF: 0.751 AC: 114155 AN: 152048 Hom.: 42938 Cov.: 31 AF XY: 0.750 AC XY: 55705 AN XY: 74314

African (AFR) AF: 0.720 AC: 29828 AN: 41428

American (AMR) AF: 0.780 AC: 11931 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2494 AN: 3472

East Asian (EAS) AF: 0.806 AC: 4167 AN: 5172

South Asian (SAS) AF: 0.669 AC: 3226 AN: 4822

European-Finnish (FIN) AF: 0.752 AC: 7946 AN: 10564

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.766 AC: 52065 AN: 67980

Other (OTH) AF: 0.760 AC: 1607 AN: 2114

Alfa AF: 0.768 Hom.: 5587

Bravo AF: 0.752

Asia WGS AF: 0.711 AC: 2476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.073
DANN	Benign	0.32
PhyloP100		-2.0
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: rs933151; hg19: chr21-45836005;