rs1612472

Variant names:

• chr21-44413102-C-T
• rs1612472
• NM_003307.4:c.2963-789C>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.2963-789C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 151,862 control chromosomes in the GnomAD database, including 38,477 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 0.71 (38477 hom., cov: 31)
• Consequence: TRPM2 NM_003307.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116
• Publications: 1 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.759 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.2963-789C>T		intron	N/A	NP_003298.2	O94759-1
	TRPM2	NM_001320350.2		c.2963-789C>T		intron	N/A	NP_001307279.2	E9PGK7
	TRPM2	NM_001433516.1		c.2963-789C>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.2963-789C>T		intron	N/A	ENSP00000381023.1	O94759-1
	TRPM2	ENST00000397932.6	TSL:1	c.2963-789C>T		intron	N/A	ENSP00000381026.2	E9PGK7
	TRPM2	ENST00000300482.9	TSL:1	c.2963-789C>T		intron	N/A	ENSP00000300482.5	O94759-1

Frequencies

GnomAD3 genomes AF: 0.707 AC: 107316 AN: 151744 Hom.: 38475 Cov.: 31

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.707 AC: 107356 AN: 151862 Hom.: 38477 Cov.: 31 AF XY: 0.705 AC XY: 52352 AN XY: 74224

African (AFR) AF: 0.584 AC: 24180 AN: 41382

American (AMR) AF: 0.742 AC: 11326 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2490 AN: 3470

East Asian (EAS) AF: 0.770 AC: 3976 AN: 5166

South Asian (SAS) AF: 0.650 AC: 3130 AN: 4816

European-Finnish (FIN) AF: 0.748 AC: 7861 AN: 10512

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.765 AC: 51988 AN: 67960

Other (OTH) AF: 0.726 AC: 1524 AN: 2100

Alfa AF: 0.737 Hom.: 15183

Bravo AF: 0.700

Asia WGS AF: 0.677 AC: 2356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.63
PhyloP100		-0.12
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: rs1612472; hg19: chr21-45832985;