rs11854949

Positions:

• chr15-50686144-T-G

Variant summary

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

The NM_017672.6(TRPM7):​c.3+387A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.078 in 152,246 control chromosomes in the GnomAD database, including 573 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 0.078 (573 hom., cov: 32)
• Consequence: TRPM7 NM_017672.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0690

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC128092252	NM_001414947.1	c.187+387A>C		intron_variant		ENST00000676296.1
TRPM7	NM_017672.6	c.3+387A>C		intron_variant		ENST00000646667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM7	ENST00000646667.1	c.3+387A>C		intron_variant			NM_017672.6	A1
	ENST00000676296.1	c.187+387A>C		intron_variant			NM_001414947.1	P1
TRPM7	ENST00000560955.5	c.3+387A>C		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.0779 AC: 11857 AN: 152128 Hom.: 571 Cov.: 32

Gnomad AFR AF: 0.0306

Gnomad AMI AF: 0.0769

Gnomad AMR AF: 0.0651

Gnomad ASJ AF: 0.0795

Gnomad EAS AF: 0.0968

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0531

Gnomad MID AF: 0.0962

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0784

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

GnomAD4 genome AF: 0.0780 AC: 11871 AN: 152246 Hom.: 573 Cov.: 32 AF XY: 0.0762 AC XY: 5674 AN XY: 74436

Gnomad4 AFR AF: 0.0306

Gnomad4 AMR AF: 0.0653

Gnomad4 ASJ AF: 0.0795

Gnomad4 EAS AF: 0.0964

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.0531

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.0833

Alfa AF: 0.0868 Hom.: 69

Bravo AF: 0.0740

Asia WGS AF: 0.148 AC: 514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	14
DANN	Benign	0.85

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: rs11854949; hg19: chr15-50978341;