Variant chr15-48207506-C-T 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.-186-28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0574 in 395,452 control chromosomes in the GnomAD database, including 3,140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.075 ( 1211 hom., cov: 32)

Exomes 𝑓: 0.047 ( 1929 hom. )

Consequence

SLC12A1
NM_000338.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0450

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:

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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=-0.53).

BP6

Variant 15-48207506-C-T is Benign according to our data. Variant chr15-48207506-C-T is described in ClinVar as [Benign]. Clinvar id is 1276462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
SLC12A1	NM_000338.3 linkuse as main transcript	c.-186-28C>T	intron_variant	ENST00000380993.8
SLC12A1	NM_001184832.2 linkuse as main transcript	c.-186-28C>T	intron_variant
SLC12A1	NM_001384136.1 linkuse as main transcript	c.-186-28C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC12A1	ENST00000380993.8 linkuse as main transcript	c.-186-28C>T		intron_variant		5	NM_000338.3	A1	Q13621-1

Frequencies

GnomAD3 genomes

AF:

0.0747

AC:

11357

AN:

152052

Hom.:

1204

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0507

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.408

Gnomad SAS

AF:

0.115

Gnomad FIN

AF:

0.00236

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00141

Gnomad OTH

AF:

0.0689

GnomAD4 exome

AF:

0.0466

AC:

11335

AN:

243282

Hom.:

1929

Cov.:

AF XY:

0.0452

AC XY:

5577

AN XY:

123432

show subpopulations

Gnomad4 AFR exome

AF:

0.172

Gnomad4 AMR exome

AF:

0.0482

Gnomad4 ASJ exome

AF:

0.000232

Gnomad4 EAS exome

AF:

0.403

Gnomad4 SAS exome

AF:

0.0808

Gnomad4 FIN exome

AF:

0.00227

Gnomad4 NFE exome

AF:

0.00169

Gnomad4 OTH exome

AF:

0.0490

GnomAD4 genome

AF:

0.0748

AC:

11377

AN:

152170

Hom.:

1211

Cov.:

AF XY:

0.0771

AC XY:

5737

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.185

Gnomad4 AMR

AF:

0.0507

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.407

Gnomad4 SAS

AF:

0.114

Gnomad4 FIN

AF:

0.00236

Gnomad4 NFE

AF:

0.00141

Gnomad4 OTH

AF:

0.0777

Alfa

AF:

0.00119

Hom.:

Bravo

AF:

0.0829

Asia WGS

AF:

0.311

AC:

1077

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 26, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

5.1

DANN

Benign

0.70

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

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