chr16-56892283-G-A

Position:

• chr16-56892283-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001126108.2(SLC12A3):​c.2419+150G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0888 in 728,526 control chromosomes in the GnomAD database, including 3,181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.088 (677 hom., cov: 32)
  • Exomes 𝑓: 0.089 (2504 hom.)
• Consequence: SLC12A3 NM_001126108.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0170

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-56892283-G-A is Benign according to our data. Variant chr16-56892283-G-A is described in ClinVar as [Benign]. Clinvar id is 1230742.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC12A3	NM_001126108.2	c.2419+150G>A		intron_variant		ENST00000563236.6	NP_001119580.2
SLC12A3	NM_000339.3	c.2446+123G>A		intron_variant			NP_000330.3
SLC12A3	NM_001126107.2	c.2443+123G>A		intron_variant			NP_001119579.2
SLC12A3	NM_001410896.1	c.2416+150G>A		intron_variant			NP_001397825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A3	ENST00000563236.6	c.2419+150G>A		intron_variant		1	NM_001126108.2	ENSP00000456149.2
SLC12A3	ENST00000438926.6	c.2446+123G>A		intron_variant		1		ENSP00000402152.2
SLC12A3	ENST00000566786.5	c.2443+123G>A		intron_variant		1		ENSP00000457552.1
SLC12A3	ENST00000262502.5	c.2416+150G>A		intron_variant		5		ENSP00000262502.5

Frequencies

GnomAD3 genomes AF: 0.0883 AC: 13413 AN: 151954 Hom.: 671 Cov.: 32

Gnomad AFR AF: 0.0740

Gnomad AMI AF: 0.0209

Gnomad AMR AF: 0.0801

Gnomad ASJ AF: 0.0810

Gnomad EAS AF: 0.0449

Gnomad SAS AF: 0.0832

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0975

Gnomad OTH AF: 0.100

GnomAD4 exome AF: 0.0889 AC: 51231 AN: 576454 Hom.: 2504 AF XY: 0.0899 AC XY: 28026 AN XY: 311800

Gnomad4 AFR exome AF: 0.0751

Gnomad4 AMR exome AF: 0.0564

Gnomad4 ASJ exome AF: 0.0845

Gnomad4 EAS exome AF: 0.0304

Gnomad4 SAS exome AF: 0.0836

Gnomad4 FIN exome AF: 0.119

Gnomad4 NFE exome AF: 0.0962

Gnomad4 OTH exome AF: 0.0927

GnomAD4 genome AF: 0.0883 AC: 13432 AN: 152072 Hom.: 677 Cov.: 32 AF XY: 0.0897 AC XY: 6665 AN XY: 74334

Gnomad4 AFR AF: 0.0743

Gnomad4 AMR AF: 0.0800

Gnomad4 ASJ AF: 0.0810

Gnomad4 EAS AF: 0.0448

Gnomad4 SAS AF: 0.0832

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.0975

Gnomad4 OTH AF: 0.0987

Alfa AF: 0.0934 Hom.: 437

Bravo AF: 0.0841

Asia WGS AF: 0.0620 AC: 215 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.2
DANN	Benign	0.73

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: rs13306677; hg19: chr16-56926195;