15-48227465-G-C

Position:

• chr15-48227465-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.724+894G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0293 in 375,746 control chromosomes in the GnomAD database, including 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 0.024 (209 hom., cov: 32)
  • Exomes 𝑓: 0.033 (518 hom.)
• Consequence: SLC12A1 NM_000338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.716

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]

LOC128966560 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC12A1	NM_000338.3	c.724+894G>C		intron_variant		ENST00000380993.8
LOC128966560	XR_932204.4	n.351C>G		non_coding_transcript_exon_variant	3/3
SLC12A1	NM_001184832.2	c.724+291G>C		intron_variant
SLC12A1	NM_001384136.1	c.724+1518G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC12A1	ENST00000380993.8	c.724+894G>C		intron_variant		5	NM_000338.3	A1

Frequencies

GnomAD3 genomes AF: 0.0240 AC: 3644 AN: 152086 Hom.: 209 Cov.: 32

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0492

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.0757

Gnomad FIN AF: 0.0187

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00778

Gnomad OTH AF: 0.0245

GnomAD4 exome AF: 0.0329 AC: 7361 AN: 223542 Hom.: 518 Cov.: 0 AF XY: 0.0352 AC XY: 4230 AN XY: 120196

Gnomad4 AFR exome AF: 0.0129

Gnomad4 AMR exome AF: 0.0593

Gnomad4 ASJ exome AF: 0.00242

Gnomad4 EAS exome AF: 0.251

Gnomad4 SAS exome AF: 0.0678

Gnomad4 FIN exome AF: 0.0176

Gnomad4 NFE exome AF: 0.00816

Gnomad4 OTH exome AF: 0.0279

GnomAD4 genome AF: 0.0239 AC: 3642 AN: 152204 Hom.: 209 Cov.: 32 AF XY: 0.0267 AC XY: 1989 AN XY: 74416

Gnomad4 AFR AF: 0.0110

Gnomad4 AMR AF: 0.0491

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.0745

Gnomad4 FIN AF: 0.0187

Gnomad4 NFE AF: 0.00778

Gnomad4 OTH AF: 0.0280

Alfa AF: 0.00370 Hom.: 1

Bravo AF: 0.0255

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.12
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs16960682; hg19: chr15-48519662;