rs12593807

Variant names:

• chr15-48254530-T-C
• rs12593807
• NM_000338.3:c.1943-1281T>C

Variant summary

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

The NM_000338.3(SLC12A1):​c.1943-1281T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 144,196 control chromosomes in the GnomAD database, including 7,525 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 0.28 (7525 hom., cov: 26)
• Consequence: SLC12A1 NM_000338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284
• Publications: 4 publications found

Genes affected

SLC12A1 (HGNC:10910): (solute carrier family 12 member 1) This gene encodes a kidney-specific sodium-potassium-chloride cotransporter that is expressed on the luminal membrane of renal epithelial cells of the thick ascending limb of Henle's loop and the macula densa. It plays a key role in concentrating urine and accounts for most of the NaCl resorption. It is sensitive to such diuretics as furosemide and bumetanide. Some Bartter-like syndromes result from defects in this gene. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional splice variants have been described but their biological validity in humans has not been experimentally proven.[provided by RefSeq, May 2010]

SLC12A1 Gene-Disease associations (from GenCC):

• antenatal Bartter syndrome

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Bartter disease type 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000338.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A1	NM_000338.3	MANE Select	c.1943-1281T>C		intron	N/A	NP_000329.2	Q13621-1
	SLC12A1	NM_001184832.2		c.1943-1281T>C		intron	N/A	NP_001171761.1	Q13621-3
	SLC12A1	NM_001384136.1		c.1943-1281T>C		intron	N/A	NP_001371065.1	A0A8I5KSK6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A1	ENST00000380993.8	TSL:5 MANE Select	c.1943-1281T>C		intron	N/A	ENSP00000370381.3	Q13621-1
	SLC12A1	ENST00000558252.5	TSL:1	n.6066-1281T>C		intron	N/A
	SLC12A1	ENST00000560692.5	TSL:1	n.6082-1281T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.276 AC: 39838 AN: 144094 Hom.: 7497 Cov.: 26

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.0501

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.192

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.277 AC: 39915 AN: 144196 Hom.: 7525 Cov.: 26 AF XY: 0.279 AC XY: 19389 AN XY: 69404

African (AFR) AF: 0.531 AC: 21052 AN: 39638

American (AMR) AF: 0.267 AC: 3641 AN: 13642

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 672 AN: 3434

East Asian (EAS) AF: 0.434 AC: 2127 AN: 4900

South Asian (SAS) AF: 0.222 AC: 1015 AN: 4580

European-Finnish (FIN) AF: 0.184 AC: 1527 AN: 8314

Middle Eastern (MID) AF: 0.199 AC: 51 AN: 256

European-Non Finnish (NFE) AF: 0.139 AC: 9238 AN: 66546

Other (OTH) AF: 0.275 AC: 547 AN: 1988

Alfa AF: 0.168 Hom.: 3378

Bravo AF: 0.289

Asia WGS AF: 0.353 AC: 1225 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.80
DANN	Benign	0.65
PhyloP100		-0.28
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: rs12593807; hg19: chr15-48546727;