15-48259397-T-G

Position:

• chr15-48259397-T-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000338.3(SLC12A1):​c.2154+86T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00544 in 932,660 control chromosomes in the GnomAD database, including 23 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 0.0049 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0056 (22 hom.)
• Consequence: SLC12A1 NM_000338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.298

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BS2: High Homozygotes in GnomAdExome4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC12A1	NM_000338.3	c.2154+86T>G		intron_variant		ENST00000380993.8	NP_000329.2
SLC12A1	NM_001184832.2	c.2154+86T>G		intron_variant			NP_001171761.1
SLC12A1	NM_001384136.1	c.2154+86T>G		intron_variant			NP_001371065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A1	ENST00000380993.8	c.2154+86T>G		intron_variant		5	NM_000338.3	ENSP00000370381.3

Frequencies

GnomAD3 genomes AF: 0.00485 AC: 738 AN: 152090 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00126

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00387

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0117

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00717

Gnomad OTH AF: 0.00527

GnomAD4 exome AF: 0.00555 AC: 4332 AN: 780452 Hom.: 22 AF XY: 0.00529 AC XY: 2191 AN XY: 414554

Gnomad4 AFR exome AF: 0.00142

Gnomad4 AMR exome AF: 0.00295

Gnomad4 ASJ exome AF: 0.000413

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000193

Gnomad4 FIN exome AF: 0.00979

Gnomad4 NFE exome AF: 0.00699

Gnomad4 OTH exome AF: 0.00531

GnomAD4 genome AF: 0.00486 AC: 739 AN: 152208 Hom.: 1 Cov.: 31 AF XY: 0.00494 AC XY: 368 AN XY: 74424

Gnomad4 AFR AF: 0.00125

Gnomad4 AMR AF: 0.00386

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0117

Gnomad4 NFE AF: 0.00718

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00374 Hom.: 0

Bravo AF: 0.00408

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.96
DANN	Benign	0.83

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: rs17428448; hg19: chr15-48551594;