rs933151

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM2	NM_003307.4	c.3147-1805C>T		intron_variant	Intron 20 of 31	ENST00000397928.6	NP_003298.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM2	ENST00000397928.6	c.3147-1805C>T		intron_variant	Intron 20 of 31	1	NM_003307.4	ENSP00000381023.1

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

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.750

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.719

Gnomad4 OTH exome AF: 0.583

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

Gnomad4 AFR AF: 0.720

Gnomad4 AMR AF: 0.780

Gnomad4 ASJ AF: 0.718

Gnomad4 EAS AF: 0.806

Gnomad4 SAS AF: 0.669

Gnomad4 FIN AF: 0.752

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.760

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.073
DANN	Benign	0.32

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

Other links and lift over

dbSNP: rs933151; hg19: chr21-45836005;