15-48232325-G-C

Variant summary

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

The NM_000338.3(SLC12A1):c.976-402G>C 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 152,150 control chromosomes in the GnomAD database, including 43,024 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 (43024 hom., cov: 32)
• Consequence: SLC12A1 NM_000338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.813

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC12A1	NM_000338.3	c.976-402G>C		intron_variant		ENST00000380993.8
SLC12A1	NM_001184832.2	c.976-402G>C		intron_variant
SLC12A1	NM_001384136.1	c.976-402G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC12A1	ENST00000380993.8	c.976-402G>C		intron_variant		5	NM_000338.3	A1

Frequencies

GnomAD3 genomes AF: 0.744 AC: 113086 AN: 152032 Hom.: 43012 Cov.: 32

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.806

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: 113140 AN: 152150 Hom.: 43024 Cov.: 32 AF XY: 0.743 AC XY: 55250 AN XY: 74368

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.757

Gnomad4 ASJ AF: 0.785

Gnomad4 EAS AF: 0.449

Gnomad4 SAS AF: 0.764

Gnomad4 FIN AF: 0.826

Gnomad4 NFE AF: 0.824

Gnomad4 OTH AF: 0.739

Alfa AF: 0.778 Hom.: 5482

Bravo AF: 0.731

Asia WGS AF: 0.614 AC: 2136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.2
Dann	Benign	0.67

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: rs1843144; hg19: chr15-48524522;