15-50586281-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_017672.6(TRPM7):c.4486+111C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 614,084 control chromosomes in the GnomAD database, including 93,939 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.56 (23564 hom., cov: 32)
  • Exomes 𝑓: 0.55 (70375 hom.)
• Consequence: TRPM7 NM_017672.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.223

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 15-50586281-G-A is Benign according to our data. Variant chr15-50586281-G-A is described in ClinVar as [Benign]. Clinvar id is 1249733.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPM7	NM_017672.6	c.4486+111C>T		intron_variant		ENST00000646667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM7	ENST00000646667.1	c.4486+111C>T		intron_variant			NM_017672.6	A1
TRPM7	ENST00000560955.5	c.4486+111C>T		intron_variant		1		P4
TRPM7	ENST00000560849.2	n.191+111C>T		intron_variant, non_coding_transcript_variant		3
TRPM7	ENST00000645282.1	n.290+111C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84345 AN: 151922 Hom.: 23548 Cov.: 32

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.595

GnomAD4 exome AF: 0.550 AC: 254159 AN: 462042 Hom.: 70375 AF XY: 0.552 AC XY: 133633 AN XY: 241978

Gnomad4 AFR exome AF: 0.538

Gnomad4 AMR exome AF: 0.613

Gnomad4 ASJ exome AF: 0.549

Gnomad4 EAS exome AF: 0.559

Gnomad4 SAS exome AF: 0.565

Gnomad4 FIN exome AF: 0.477

Gnomad4 NFE exome AF: 0.554

Gnomad4 OTH exome AF: 0.551

GnomAD4 genome AF: 0.555 AC: 84411 AN: 152042 Hom.: 23564 Cov.: 32 AF XY: 0.555 AC XY: 41266 AN XY: 74306

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.623

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.570

Gnomad4 SAS AF: 0.560

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.592

Alfa AF: 0.549 Hom.: 3593

Bravo AF: 0.565

Asia WGS AF: 0.556 AC: 1932 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	1.8
Dann	Benign	0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs539383; hg19: chr15-50878478; COSMIC: COSV57915419; COSMIC: COSV57915419;