rs711746

Positions:

• chr16-56912892-T-C
• chr16-56912892-T-G

Variant summary

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

The NM_001126108.2(SLC12A3):​c.2925-372T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 151,786 control chromosomes in the GnomAD database, including 29,201 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 0.61 (29201 hom., cov: 30)
• Consequence: SLC12A3 NM_001126108.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

Genes affected

SLC12A3 (HGNC:10912): (solute carrier family 12 member 3) This gene encodes a renal thiazide-sensitive sodium-chloride cotransporter that is important for electrolyte homeostasis. This cotransporter mediates sodium and chloride reabsorption in the distal convoluted tubule. Mutations in this gene cause Gitelman syndrome, a disease similar to Bartter's syndrome, that is characterized by hypokalemic alkalosis combined with hypomagnesemia, low urinary calcium, and increased renin activity associated with normal blood pressure. This cotransporter is the target for thiazide diuretics that are used for treating high blood pressure. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC12A3	NM_001126108.2	c.2925-372T>C		intron_variant		ENST00000563236.6
SLC12A3	NM_000339.3	c.2952-372T>C		intron_variant
SLC12A3	NM_001126107.2	c.2949-372T>C		intron_variant
SLC12A3	NM_001410896.1	c.2922-372T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC12A3	ENST00000563236.6	c.2925-372T>C		intron_variant		1	NM_001126108.2	A1

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92426 AN: 151668 Hom.: 29181 Cov.: 30

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.615

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

GnomAD4 genome AF: 0.609 AC: 92491 AN: 151786 Hom.: 29201 Cov.: 30 AF XY: 0.608 AC XY: 45056 AN XY: 74166

Gnomad4 AFR AF: 0.777

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.562

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.610

Alfa AF: 0.562 Hom.: 31868

Bravo AF: 0.610

Asia WGS AF: 0.460 AC: 1599 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.38

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: rs711746; hg19: chr16-56946804;