Variant 15-48255779-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000338.3(SLC12A1):c.1943-32T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,388,998 control chromosomes in the GnomAD database, including 49,425 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 13450 hom., cov: 32)

Exomes 𝑓: 0.22 ( 35975 hom. )

Consequence

SLC12A1
NM_000338.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.898

Variant links:

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 links:

SLC12A1 (HGNC:):

SLC12A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 15-48255779-T-C is Benign according to our data. Variant chr15-48255779-T-C is described in ClinVar as [Benign]. Clinvar id is 1278170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
SLC12A1	NM_000338.3 linkuse as main transcript	c.1943-32T>C	intron_variant	ENST00000380993.8	NP_000329.2	Q13621-1Q8IUN5
SLC12A1	NM_001184832.2 linkuse as main transcript	c.1943-32T>C	intron_variant		NP_001171761.1	Q13621-3B4DPF4
SLC12A1	NM_001384136.1 linkuse as main transcript	c.1943-32T>C	intron_variant		NP_001371065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A1	ENST00000380993.8 linkuse as main transcript	c.1943-32T>C		intron_variant		5	NM_000338.3	ENSP00000370381.3		Q13621-1

Frequencies

GnomAD3 genomes

AF:

0.355

AC:

53937

AN:

152012

Hom.:

13404

Cov.:

show subpopulations

Gnomad AFR

AF:

0.703

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.295

Gnomad ASJ

AF:

0.229

Gnomad EAS

AF:

0.425

Gnomad SAS

AF:

0.257

Gnomad FIN

AF:

0.208

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.193

Gnomad OTH

AF:

0.331

GnomAD3 exomes

AF:

0.268

AC:

50824

AN:

189442

Hom.:

8500

AF XY:

0.257

AC XY:

25719

AN XY:

100026

show subpopulations

Gnomad AFR exome

AF:

0.713

Gnomad AMR exome

AF:

0.296

Gnomad ASJ exome

AF:

0.224

Gnomad EAS exome

AF:

0.421

Gnomad SAS exome

AF:

0.241

Gnomad FIN exome

AF:

0.217

Gnomad NFE exome

AF:

0.192

Gnomad OTH exome

AF:

0.248

GnomAD4 exome

AF:

0.221

AC:

272929

AN:

1236868

Hom.:

35975

Cov.:

AF XY:

0.219

AC XY:

135936

AN XY:

619978

show subpopulations

Gnomad4 AFR exome

AF:

0.722

Gnomad4 AMR exome

AF:

0.299

Gnomad4 ASJ exome

AF:

0.226

Gnomad4 EAS exome

AF:

0.451

Gnomad4 SAS exome

AF:

0.232

Gnomad4 FIN exome

AF:

0.220

Gnomad4 NFE exome

AF:

0.190

Gnomad4 OTH exome

AF:

0.249

GnomAD4 genome

AF:

0.355

AC:

54047

AN:

152130

Hom.:

13450

Cov.:

AF XY:

0.352

AC XY:

26172

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.703

Gnomad4 AMR

AF:

0.295

Gnomad4 ASJ

AF:

0.229

Gnomad4 EAS

AF:

0.424

Gnomad4 SAS

AF:

0.256

Gnomad4 FIN

AF:

0.208

Gnomad4 NFE

AF:

0.193

Gnomad4 OTH

AF:

0.337

Alfa

AF:

0.224

Hom.:

2807

Bravo

AF:

0.377

Asia WGS

AF:

0.389

AC:

1351

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.0

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over