rs2279366

Variant names:

• chr15-48249830-G-A
• rs2279366
• NM_000338.3:c.1786+154G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-48249830-G-A
• chr15-48249830-G-C
• chr15-48249830-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_000338.3(SLC12A1):​c.1786+154G>A 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 152,076 control chromosomes in the GnomAD database, including 8,788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.30 (8788 hom., cov: 33)
• Consequence: SLC12A1 NM_000338.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.24
• Publications: 9 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), PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 15-48249830-G-A is Benign according to our data. Variant chr15-48249830-G-A is described in ClinVar as Benign. ClinVar VariationId is 1287765.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 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.1786+154G>A		intron	N/A	NP_000329.2	Q13621-1
	SLC12A1	NM_001184832.2		c.1786+154G>A		intron	N/A	NP_001171761.1	Q13621-3
	SLC12A1	NM_001384136.1		c.1786+154G>A		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.1786+154G>A		intron	N/A	ENSP00000370381.3	Q13621-1
	SLC12A1	ENST00000558252.5	TSL:1	n.5909+154G>A		intron	N/A
	SLC12A1	ENST00000560692.5	TSL:1	n.5925+154G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45442 AN: 151958 Hom.: 8756 Cov.: 33

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.299 AC: 45528 AN: 152076 Hom.: 8788 Cov.: 33 AF XY: 0.300 AC XY: 22334 AN XY: 74350

African (AFR) AF: 0.524 AC: 21728 AN: 41438

American (AMR) AF: 0.274 AC: 4193 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 775 AN: 3470

East Asian (EAS) AF: 0.534 AC: 2759 AN: 5168

South Asian (SAS) AF: 0.318 AC: 1529 AN: 4814

European-Finnish (FIN) AF: 0.194 AC: 2059 AN: 10590

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11721 AN: 67998

Other (OTH) AF: 0.299 AC: 631 AN: 2110

Alfa AF: 0.213 Hom.: 6942

Bravo AF: 0.315

Asia WGS AF: 0.434 AC: 1506 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Benign	0.49
PhyloP100		3.2
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: rs2279366; hg19: chr15-48542027;