rs2291340

Variant names:

• chr15-48255779-T-A
• rs2291340
• NM_000338.3:c.1943-32T>A

Your query was ambiguous. Multiple possible variants found:

• chr15-48255779-T-A
• chr15-48255779-T-C
• chr15-48255779-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000338.3(SLC12A1):​c.1943-32T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC12A1 NM_000338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.898
• Publications: 8 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A1	NM_000338.3	c.1943-32T>A		intron_variant	Intron 15 of 26	ENST00000380993.8	NP_000329.2
SLC12A1	NM_001184832.2	c.1943-32T>A		intron_variant	Intron 15 of 26		NP_001171761.1
SLC12A1	NM_001384136.1	c.1943-32T>A		intron_variant	Intron 15 of 26		NP_001371065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A1	ENST00000380993.8	c.1943-32T>A		intron_variant	Intron 15 of 26	5	NM_000338.3	ENSP00000370381.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1238568 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 620802

African (AFR) AF: 0.00 AC: 0 AN: 28962

American (AMR) AF: 0.00 AC: 0 AN: 37938

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24072

East Asian (EAS) AF: 0.00 AC: 0 AN: 36866

South Asian (SAS) AF: 0.00 AC: 0 AN: 75872

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50982

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5388

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 925566

Other (OTH) AF: 0.00 AC: 0 AN: 52922

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.8
DANN	Benign	0.79
PhyloP100		-0.90

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: rs2291340; hg19: chr15-48547976;