rs4818917

Positions:

• chr21-44379397-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003307.4(TRPM2):​c.1215+200T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 151,894 control chromosomes in the GnomAD database, including 4,865 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 0.24 (4865 hom., cov: 32)
• Consequence: TRPM2 NM_003307.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.91

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPM2	NM_003307.4	c.1215+200T>C		intron_variant		ENST00000397928.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM2	ENST00000397928.6	c.1215+200T>C		intron_variant		1	NM_003307.4	P1

Frequencies

GnomAD3 genomes AF: 0.244 AC: 36990 AN: 151776 Hom.: 4843 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.244 AC: 37073 AN: 151894 Hom.: 4865 Cov.: 32 AF XY: 0.243 AC XY: 18071 AN XY: 74246

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.195

Alfa AF: 0.218 Hom.: 878

Bravo AF: 0.247

Asia WGS AF: 0.173 AC: 605 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	0.26
DANN	Benign	0.26

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: rs4818917; hg19: chr21-45799280;