rs2414059

Variant names:

• chr15-50581147-T-A
• rs2414059
• NM_017672.6:c.4558-239A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017672.6(TRPM7):​c.4558-239A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,986 control chromosomes in the GnomAD database, including 17,718 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 0.48 (17718 hom., cov: 32)
• Consequence: TRPM7 NM_017672.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446
• Publications: 15 publications found

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]

TRPM7 Gene-Disease associations (from GenCC):

• hypomagnesemia, seizures, and intellectual disability

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• autosomal dominant macrothrombocytopenia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• macrothrombocytopenia, isolated

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• amyotrophic lateral sclerosis-parkinsonism-dementia complex

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017672.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM7	NM_017672.6	MANE Select	c.4558-239A>T		intron	N/A	NP_060142.3
	TRPM7	NM_001301212.2		c.4555-239A>T		intron	N/A	NP_001288141.1
	TRPM7	NR_149152.2		n.4772-239A>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM7	ENST00000646667.1	MANE Select	c.4558-239A>T		intron	N/A	ENSP00000495860.1
	TRPM7	ENST00000560955.5	TSL:1	c.4555-239A>T		intron	N/A	ENSP00000453277.1
	TRPM7	ENST00000558444.5	TSL:3	n.31-239A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72838 AN: 151868 Hom.: 17703 Cov.: 32

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.480 AC: 72898 AN: 151986 Hom.: 17718 Cov.: 32 AF XY: 0.481 AC XY: 35745 AN XY: 74276

African (AFR) AF: 0.519 AC: 21515 AN: 41432

American (AMR) AF: 0.558 AC: 8516 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1648 AN: 3468

East Asian (EAS) AF: 0.471 AC: 2440 AN: 5178

South Asian (SAS) AF: 0.438 AC: 2113 AN: 4826

European-Finnish (FIN) AF: 0.419 AC: 4413 AN: 10524

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.449 AC: 30541 AN: 67970

Other (OTH) AF: 0.511 AC: 1080 AN: 2112

Alfa AF: 0.454 Hom.: 1938

Bravo AF: 0.495

Asia WGS AF: 0.411 AC: 1431 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.3
DANN	Benign	0.70
PhyloP100		0.45
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: rs2414059; hg19: chr15-50873344;