rs11854679

Variant names:

• chr15-48265376-T-C
• rs11854679
• NM_000338.3:c.2155-2185T>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.2155-2185T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,104 control chromosomes in the GnomAD database, including 8,450 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 0.30 (8450 hom., cov: 33)
• Consequence: SLC12A1 NM_000338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181
• Publications: 1 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):

• Bartter disease type 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• antenatal Bartter syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A1	NM_000338.3	MANE Select	c.2155-2185T>C		intron	N/A	NP_000329.2
	SLC12A1	NM_001184832.2		c.2155-2185T>C		intron	N/A	NP_001171761.1
	SLC12A1	NM_001384136.1		c.2155-2185T>C		intron	N/A	NP_001371065.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A1	ENST00000380993.8	TSL:5 MANE Select	c.2155-2185T>C		intron	N/A	ENSP00000370381.3
	SLC12A1	ENST00000558252.5	TSL:1	n.6278-2185T>C		intron	N/A
	SLC12A1	ENST00000560692.5	TSL:1	n.6294-2185T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45408 AN: 151986 Hom.: 8419 Cov.: 33

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.299 AC: 45502 AN: 152104 Hom.: 8450 Cov.: 33 AF XY: 0.297 AC XY: 22089 AN XY: 74352

African (AFR) AF: 0.519 AC: 21513 AN: 41482

American (AMR) AF: 0.275 AC: 4202 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 763 AN: 3468

East Asian (EAS) AF: 0.412 AC: 2132 AN: 5178

South Asian (SAS) AF: 0.238 AC: 1146 AN: 4824

European-Finnish (FIN) AF: 0.208 AC: 2204 AN: 10572

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12817 AN: 67994

Other (OTH) AF: 0.291 AC: 616 AN: 2114

Alfa AF: 0.269 Hom.: 870

Bravo AF: 0.313

Asia WGS AF: 0.373 AC: 1296 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.62
PhyloP100		0.18
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: rs11854679; hg19: chr15-48557573;