rs11635825

chr15-50662750-T-C

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.83+217A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,130 control chromosomes in the GnomAD database, including 1,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1492 hom., cov: 32)
• Consequence: TRPM7 NM_017672.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.751

Genes affected

LOC128092252 (HGNC:):

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=-0.91).
• BP6: Variant 15-50662750-T-C is Benign according to our data. Variant chr15-50662750-T-C is described in ClinVar as [Benign]. Clinvar id is 1232550.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC128092252	NM_001414947.1	c.267+217A>G		intron_variant		ENST00000676296.1
TRPM7	NM_017672.6	c.83+217A>G		intron_variant		ENST00000646667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM7	ENST00000646667.1	c.83+217A>G		intron_variant			NM_017672.6	A1
	ENST00000676296.1	c.267+217A>G		intron_variant			NM_001414947.1	P1
TRPM7	ENST00000560955.5	c.83+217A>G		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20994 AN: 152012 Hom.: 1491 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.0669

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.138 AC: 21016 AN: 152130 Hom.: 1492 Cov.: 32 AF XY: 0.135 AC XY: 10064 AN XY: 74380

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.0998

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.0669

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.150

Alfa AF: 0.144 Hom.: 1215

Bravo AF: 0.139

Asia WGS AF: 0.180 AC: 627 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

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.27
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: rs11635825; hg19: chr15-50954947;