rs1531916

Variant names:

• chr15-48234074-G-A
• rs1531916
• NM_000338.3:c.1088-803G>A

Variant summary

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

The NM_000338.3(SLC12A1):​c.1088-803G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,112 control chromosomes in the GnomAD database, including 43,064 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 0.74 (43064 hom., cov: 32)
• Consequence: SLC12A1 NM_000338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.228
• 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):

• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A1	NM_000338.3	c.1088-803G>A		intron_variant	Intron 8 of 26	ENST00000380993.8	NP_000329.2
SLC12A1	NM_001184832.2	c.1088-803G>A		intron_variant	Intron 8 of 26		NP_001171761.1
SLC12A1	NM_001384136.1	c.1088-803G>A		intron_variant	Intron 8 of 26		NP_001371065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A1	ENST00000380993.8	c.1088-803G>A		intron_variant	Intron 8 of 26	5	NM_000338.3	ENSP00000370381.3

Frequencies

GnomAD3 genomes AF: 0.744 AC: 113148 AN: 151994 Hom.: 43050 Cov.: 32

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.762

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.746

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

GnomAD4 genome AF: 0.744 AC: 113205 AN: 152112 Hom.: 43064 Cov.: 32 AF XY: 0.744 AC XY: 55287 AN XY: 74358

African (AFR) AF: 0.616 AC: 25554 AN: 41452

American (AMR) AF: 0.757 AC: 11567 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.785 AC: 2727 AN: 3472

East Asian (EAS) AF: 0.448 AC: 2315 AN: 5164

South Asian (SAS) AF: 0.763 AC: 3680 AN: 4824

European-Finnish (FIN) AF: 0.826 AC: 8753 AN: 10596

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.824 AC: 56045 AN: 68010

Other (OTH) AF: 0.739 AC: 1557 AN: 2108

Alfa AF: 0.794 Hom.: 70310

Bravo AF: 0.732

Asia WGS AF: 0.616 AC: 2142 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.16
PhyloP100		0.23
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: rs1531916; hg19: chr15-48526271;