rs2279366

Positions:

• chr15-48249830-G-A
• chr15-48249830-G-C
• chr15-48249830-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_000338.3(SLC12A1):​c.1786+154G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,076 control chromosomes in the GnomAD database, including 8,788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.30 (8788 hom., cov: 33)
• Consequence: SLC12A1 NM_000338.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.24

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=-0.44).
• BP6: Variant 15-48249830-G-A is Benign according to our data. Variant chr15-48249830-G-A is described in ClinVar as [Benign]. Clinvar id is 1287765.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC12A1	NM_000338.3	c.1786+154G>A		intron_variant		ENST00000380993.8
SLC12A1	NM_001184832.2	c.1786+154G>A		intron_variant
SLC12A1	NM_001384136.1	c.1786+154G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC12A1	ENST00000380993.8	c.1786+154G>A		intron_variant		5	NM_000338.3	A1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45442 AN: 151958 Hom.: 8756 Cov.: 33

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.299 AC: 45528 AN: 152076 Hom.: 8788 Cov.: 33 AF XY: 0.300 AC XY: 22334 AN XY: 74350

Gnomad4 AFR AF: 0.524

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.534

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.299

Alfa AF: 0.201 Hom.: 4730

Bravo AF: 0.315

Asia WGS AF: 0.434 AC: 1506 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Benign	0.49

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: rs2279366; hg19: chr15-48542027;