rs8048695

Variant names:

• chr16-56877074-G-A
• rs8048695
• NM_001126108.2:c.1096-1003G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_001126108.2(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 NM_001126108.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• Gitelman syndrome

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001126108.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A3	NM_001126108.2	MANE Select	c.1096-1003G>A		intron	N/A	NP_001119580.2
	SLC12A3	NM_000339.3		c.1096-1003G>A		intron	N/A	NP_000330.3
	SLC12A3	NM_001126107.2		c.1093-1003G>A		intron	N/A	NP_001119579.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A3	ENST00000563236.6	TSL:1 MANE Select	c.1096-1003G>A		intron	N/A	ENSP00000456149.2
	SLC12A3	ENST00000438926.6	TSL:1	c.1096-1003G>A		intron	N/A	ENSP00000402152.2
	SLC12A3	ENST00000566786.5	TSL:1	c.1093-1003G>A		intron	N/A	ENSP00000457552.1

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

African (AFR) AF: 0.126 AC: 5216 AN: 41528

American (AMR) AF: 0.198 AC: 3033 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 722 AN: 3470

East Asian (EAS) AF: 0.188 AC: 973 AN: 5164

South Asian (SAS) AF: 0.199 AC: 957 AN: 4816

European-Finnish (FIN) AF: 0.127 AC: 1352 AN: 10614

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12429 AN: 67988

Other (OTH) AF: 0.183 AC: 386 AN: 2110

Alfa AF: 0.169 Hom.: 1750

Bravo AF: 0.171

Asia WGS AF: 0.183 AC: 635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.4
DANN	Benign	0.77
PhyloP100		0.049
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: rs8048695; hg19: chr16-56910986;