rs2163098

Positions:

• chr15-50614301-C-G

Variant summary

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

The NM_017672.6(TRPM7):​c.1495-38G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0334 in 1,545,672 control chromosomes in the GnomAD database, including 1,065 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 0.029 (90 hom., cov: 32)
  • Exomes 𝑓: 0.034 (975 hom.)
• Consequence: TRPM7 NM_017672.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.786

Genes affected

TRPM7 (HGNC:17994): (transient receptor potential cation channel subfamily M member 7) This gene belongs to the melastatin subfamily of transient receptor potential family of ion channels. The protein encoded by this gene is both an ion channel and a serine/threonine protein kinase. The kinase activity is essential for the ion channel function, which serves to increase intracellular calcium levels and to help regulate magnesium ion homeostasis. The encoded protein is involved in cytoskeletal organization, cell adhesion, cell migration and organogenesis. Defects in this gene are a cause of amyotrophic lateral sclerosis-parkinsonism/dementia complex of Guam. The gene may also be associated with defects of cardiac function. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPM7	NM_017672.6	c.1495-38G>C		intron_variant		ENST00000646667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM7	ENST00000646667.1	c.1495-38G>C		intron_variant			NM_017672.6	A1
TRPM7	ENST00000560638.1	c.106-38G>C		intron_variant		1
TRPM7	ENST00000560955.5	c.1495-38G>C		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.0287 AC: 4363 AN: 152130 Hom.: 90 Cov.: 32

Gnomad AFR AF: 0.0123

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0451

Gnomad ASJ AF: 0.0832

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0245

Gnomad FIN AF: 0.0124

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0366

Gnomad OTH AF: 0.0426

GnomAD3 exomes AF: 0.0316 AC: 6461 AN: 204634 Hom.: 130 AF XY: 0.0330 AC XY: 3649 AN XY: 110602

Gnomad AFR exome AF: 0.0123

Gnomad AMR exome AF: 0.0343

Gnomad ASJ exome AF: 0.0919

Gnomad EAS exome AF: 0.000185

Gnomad SAS exome AF: 0.0292

Gnomad FIN exome AF: 0.0108

Gnomad NFE exome AF: 0.0393

Gnomad OTH exome AF: 0.0418

GnomAD4 exome AF: 0.0339 AC: 47256 AN: 1393424 Hom.: 975 Cov.: 26 AF XY: 0.0346 AC XY: 23896 AN XY: 691242

Gnomad4 AFR exome AF: 0.0118

Gnomad4 AMR exome AF: 0.0345

Gnomad4 ASJ exome AF: 0.0860

Gnomad4 EAS exome AF: 0.000128

Gnomad4 SAS exome AF: 0.0287

Gnomad4 FIN exome AF: 0.0110

Gnomad4 NFE exome AF: 0.0358

Gnomad4 OTH exome AF: 0.0367

GnomAD4 genome AF: 0.0286 AC: 4359 AN: 152248 Hom.: 90 Cov.: 32 AF XY: 0.0283 AC XY: 2105 AN XY: 74436

Gnomad4 AFR AF: 0.0123

Gnomad4 AMR AF: 0.0450

Gnomad4 ASJ AF: 0.0832

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0245

Gnomad4 FIN AF: 0.0124

Gnomad4 NFE AF: 0.0366

Gnomad4 OTH AF: 0.0422

Alfa AF: 0.0378 Hom.: 26

Bravo AF: 0.0296

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.47
DANN	Benign	0.54

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: rs2163098; hg19: chr15-50906498;