rs12594698

Positions:

• chr15-48282759-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000338.3(SLC12A1):​c.2486-2347C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 151,970 control chromosomes in the GnomAD database, including 6,727 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 0.28 (6727 hom., cov: 32)
• Consequence: SLC12A1 NM_000338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC12A1	NM_000338.3	c.2486-2347C>T		intron_variant		ENST00000380993.8	NP_000329.2
SLC12A1	NM_001184832.2	c.2486-2347C>T		intron_variant			NP_001171761.1
SLC12A1	NM_001384136.1	c.2486-2347C>T		intron_variant			NP_001371065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A1	ENST00000380993.8	c.2486-2347C>T		intron_variant		5	NM_000338.3	ENSP00000370381	A1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41712 AN: 151852 Hom.: 6699 Cov.: 32

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.275 AC: 41794 AN: 151970 Hom.: 6727 Cov.: 32 AF XY: 0.274 AC XY: 20353 AN XY: 74280

Gnomad4 AFR AF: 0.434

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.412

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.208

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.276

Alfa AF: 0.212 Hom.: 1580

Bravo AF: 0.286

Asia WGS AF: 0.370 AC: 1287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	2.0
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs12594698; hg19: chr15-48574956;