rs2289116

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001126108.2(SLC12A3):c.2857-17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,611,780 control chromosomes in the GnomAD database, including 11,073 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1550 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9523 hom. )

Consequence

SLC12A3
NM_001126108.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.471

Variant links:

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]

SLC12A3 links:

MIR6863 (HGNC:49942): (microRNA 6863) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR6863 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 16-56904378-G-A is Benign according to our data. Variant chr16-56904378-G-A is described in ClinVar as [Benign]. Clinvar id is 255890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56904378-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A3	NM_001126108.2 link	c.2857-17G>A		intron_variant	Intron 24 of 25	ENST00000563236.6	NP_001119580.2	P55017-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A3	ENST00000563236.6 link	c.2857-17G>A		intron_variant	Intron 24 of 25	1	NM_001126108.2	ENSP00000456149.2		P55017-1

Frequencies

GnomAD3 genomes

AF:

0.134

AC:

20447

AN:

152130

Hom.:

1541

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.0209

Gnomad AMR

AF:

0.151

Gnomad ASJ

AF:

0.0881

Gnomad EAS

AF:

0.0712

Gnomad SAS

AF:

0.0909

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.109

Gnomad OTH

AF:

0.154

GnomAD3 exomes

AF:

0.122

AC:

30584

AN:

251486

Hom.:

2014

AF XY:

0.117

AC XY:

15925

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.191

Gnomad AMR exome

AF:

0.188

Gnomad ASJ exome

AF:

0.0917

Gnomad EAS exome

AF:

0.0732

Gnomad SAS exome

AF:

0.0942

Gnomad FIN exome

AF:

0.123

Gnomad NFE exome

AF:

0.109

Gnomad OTH exome

AF:

0.127

GnomAD4 exome

AF:

0.112

AC:

162796

AN:

1459532

Hom.:

9523

Cov.:

AF XY:

0.111

AC XY:

80410

AN XY:

726176

show subpopulations

Gnomad4 AFR exome

AF:

0.192

Gnomad4 AMR exome

AF:

0.177

Gnomad4 ASJ exome

AF:

0.0929

Gnomad4 EAS exome

AF:

0.0666

Gnomad4 SAS exome

AF:

0.0928

Gnomad4 FIN exome

AF:

0.123

Gnomad4 NFE exome

AF:

0.109

Gnomad4 OTH exome

AF:

0.113

GnomAD4 genome

AF:

0.135

AC:

20485

AN:

152248

Hom.:

1550

Cov.:

AF XY:

0.134

AC XY:

10006

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.191

Gnomad4 AMR

AF:

0.151

Gnomad4 ASJ

AF:

0.0881

Gnomad4 EAS

AF:

0.0715

Gnomad4 SAS

AF:

0.0909

Gnomad4 FIN

AF:

0.123

Gnomad4 NFE

AF:

0.109

Gnomad4 OTH

AF:

0.152

Alfa

AF:

0.120

Hom.:

220

Bravo

AF:

0.142

Asia WGS

AF:

0.0920

AC:

317

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Aug 06, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 28008009, 14578305) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial hypokalemia-hypomagnesemia

Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over