rs8048695

Positions:

• chr16-56877074-G-A
• chr16-56877074-G-C

Variant summary

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

The ENST00000563236.6(SLC12A3):​c.1096-1003G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,178 control chromosomes in the GnomAD database, including 2,197 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 0.17 (2197 hom., cov: 32)
• Consequence: SLC12A3 ENST00000563236.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC12A3	NM_001126108.2	c.1096-1003G>A		intron_variant		ENST00000563236.6	NP_001119580.2
SLC12A3	NM_000339.3	c.1096-1003G>A		intron_variant			NP_000330.3
SLC12A3	NM_001126107.2	c.1093-1003G>A		intron_variant			NP_001119579.2
SLC12A3	NM_001410896.1	c.1093-1003G>A		intron_variant			NP_001397825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A3	ENST00000563236.6	c.1096-1003G>A		intron_variant		1	NM_001126108.2	ENSP00000456149	A1
SLC12A3	ENST00000438926.6	c.1096-1003G>A		intron_variant		1		ENSP00000402152	A1
SLC12A3	ENST00000566786.5	c.1093-1003G>A		intron_variant		1		ENSP00000457552	P4
SLC12A3	ENST00000262502.5	c.1093-1003G>A		intron_variant		5		ENSP00000262502	A1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25460 AN: 152060 Hom.: 2193 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.167 AC: 25462 AN: 152178 Hom.: 2197 Cov.: 32 AF XY: 0.167 AC XY: 12437 AN XY: 74402

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.183

Alfa AF: 0.167 Hom.: 1406

Bravo AF: 0.171

Asia WGS AF: 0.183 AC: 635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.4
DANN	Benign	0.77

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: rs8048695; hg19: chr16-56910986;