rs7867868

Variant names:

• chr9-74831958-C-T
• rs7867868
• NM_017662.5:c.669+2040G>A

Variant summary

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

The NM_017662.5(TRPM6):​c.669+2040G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 151,926 control chromosomes in the GnomAD database, including 7,291 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 0.30 (7291 hom., cov: 32)
• Consequence: TRPM6 NM_017662.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730
• Publications: 6 publications found

Genes affected

TRPM6 (HGNC:17995): (transient receptor potential cation channel subfamily M member 6) This gene is predominantly expressed in the kidney and colon, and encodes a protein containing an ion channel domain and a protein kinase domain. It is crucial for magnesium homeostasis, and plays an essential role in epithelial magnesium transport and in the active magnesium absorption in the gut and kidney. Mutations in this gene are associated with hypomagnesemia with secondary hypocalcemia. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Apr 2010]

TRPM6 Gene-Disease associations (from GenCC):

• intestinal hypomagnesemia 1

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017662.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM6	NM_017662.5	MANE Select	c.669+2040G>A		intron	N/A	NP_060132.3
	TRPM6	NM_001177310.2		c.654+2040G>A		intron	N/A	NP_001170781.1	Q9BX84-2
	TRPM6	NM_001177311.2		c.654+2040G>A		intron	N/A	NP_001170782.1	Q9BX84-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM6	ENST00000360774.6	TSL:1 MANE Select	c.669+2040G>A		intron	N/A	ENSP00000354006.1	Q9BX84-1
	TRPM6	ENST00000361255.7	TSL:1	c.654+2040G>A		intron	N/A	ENSP00000354962.3	Q9BX84-3
	TRPM6	ENST00000449912.6	TSL:1	c.654+2040G>A		intron	N/A	ENSP00000396672.2	Q9BX84-2

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45476 AN: 151808 Hom.: 7296 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.0121

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.299 AC: 45468 AN: 151926 Hom.: 7291 Cov.: 32 AF XY: 0.293 AC XY: 21780 AN XY: 74246

African (AFR) AF: 0.259 AC: 10727 AN: 41424

American (AMR) AF: 0.291 AC: 4436 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1280 AN: 3470

East Asian (EAS) AF: 0.0122 AC: 63 AN: 5180

South Asian (SAS) AF: 0.149 AC: 718 AN: 4824

European-Finnish (FIN) AF: 0.333 AC: 3506 AN: 10526

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23594 AN: 67946

Other (OTH) AF: 0.334 AC: 702 AN: 2104

Alfa AF: 0.342 Hom.: 14437

Bravo AF: 0.295

Asia WGS AF: 0.0850 AC: 296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	8.0
DANN	Benign	0.74
PhyloP100		0.073
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: rs7867868; hg19: chr9-77446874;