rs6493312

Variant names:

• chr15-48250359-C-A
• rs6493312
• NM_000338.3:c.1786+683C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-48250359-C-A
• chr15-48250359-C-T

Variant summary

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

The NM_000338.3(SLC12A1):​c.1786+683C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,090 control chromosomes in the GnomAD database, including 2,988 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 0.14 (2988 hom., cov: 32)
• Consequence: SLC12A1 NM_000338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A1	NM_000338.3	c.1786+683C>A		intron_variant	Intron 14 of 26	ENST00000380993.8	NP_000329.2
SLC12A1	NM_001184832.2	c.1786+683C>A		intron_variant	Intron 14 of 26		NP_001171761.1
SLC12A1	NM_001384136.1	c.1786+683C>A		intron_variant	Intron 14 of 26		NP_001371065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A1	ENST00000380993.8	c.1786+683C>A		intron_variant	Intron 14 of 26	5	NM_000338.3	ENSP00000370381.3

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21723 AN: 151972 Hom.: 2973 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0932

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.0980

Gnomad FIN AF: 0.0739

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.0415

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.143 AC: 21783 AN: 152090 Hom.: 2988 Cov.: 32 AF XY: 0.143 AC XY: 10659 AN XY: 74356

African (AFR) AF: 0.346 AC: 14329 AN: 41406

American (AMR) AF: 0.0932 AC: 1425 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 99 AN: 3472

East Asian (EAS) AF: 0.305 AC: 1577 AN: 5176

South Asian (SAS) AF: 0.0978 AC: 472 AN: 4824

European-Finnish (FIN) AF: 0.0739 AC: 784 AN: 10602

Middle Eastern (MID) AF: 0.0685 AC: 20 AN: 292

European-Non Finnish (NFE) AF: 0.0416 AC: 2826 AN: 68014

Other (OTH) AF: 0.110 AC: 232 AN: 2110

Alfa AF: 0.0697 Hom.: 958

Bravo AF: 0.153

Asia WGS AF: 0.208 AC: 724 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.25
DANN	Benign	0.51
PhyloP100		-2.0
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: rs6493312; hg19: chr15-48542556;