Genetic Variant SLC12A1:n.3140G>C (chr15-48227465-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000560692.5(SLC12A1):n.3140G>C variant causes a non coding transcript exon 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
ENST00000560692.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.716

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

Bartter disease type 1
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
antenatal Bartter syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SLC12A1 links:

LOC128966560 (HGNC:):

LOC128966560 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein
SLC12A1	NM_000338.3 link	c.724+894G>C	intron_variant	Intron 5 of 26	ENST00000380993.8	NP_000329.2
LOC128966560	XR_932204.4 link	n.351C>G	non_coding_transcript_exon_variant	Exon 3 of 3
SLC12A1	NM_001184832.2 link	c.724+291G>C	intron_variant	Intron 5 of 26		NP_001171761.1
SLC12A1	NM_001384136.1 link	c.724+1518G>C	intron_variant	Intron 5 of 26		NP_001371065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A1	ENST00000380993.8 link	c.724+894G>C		intron_variant	Intron 5 of 26	5	NM_000338.3	ENSP00000370381.3

Frequencies

GnomAD3 genomes

AF:

0.0240

AC:

3644

AN:

152086

Hom.:

209

Cov.:

show subpopulations

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.:

AF XY:

0.0352

AC XY:

4230

AN XY:

120196

show subpopulations

African (AFR)

AF:

0.0129

AC:

AN:

6338

American (AMR)

AF:

0.0593

AC:

597

AN:

10060

Ashkenazi Jewish (ASJ)

AF:

0.00242

AC:

AN:

6186

East Asian (EAS)

AF:

0.251

AC:

2818

AN:

11240

South Asian (SAS)

AF:

0.0678

AC:

2235

AN:

32958

European-Finnish (FIN)

AF:

0.0176

AC:

188

AN:

10706

Middle Eastern (MID)

AF:

0.00576

AC:

AN:

868

European-Non Finnish (NFE)

AF:

0.00816

AC:

1087

AN:

133210

Other (OTH)

AF:

0.0279

AC:

334

AN:

11976

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

304

608

913

1217

1521

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

228

304

380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0239

AC:

3642

AN:

152204

Hom.:

209

Cov.:

AF XY:

0.0267

AC XY:

1989

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0110

AC:

457

AN:

41536

American (AMR)

AF:

0.0491

AC:

750

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3468

East Asian (EAS)

AF:

0.246

AC:

1271

AN:

5164

South Asian (SAS)

AF:

0.0745

AC:

359

AN:

4820

European-Finnish (FIN)

AF:

0.0187

AC:

198

AN:

10590

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00778

AC:

529

AN:

68026

Other (OTH)

AF:

0.0280

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

171

342

513

684

855

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00370

Hom.:

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

(source)

DANN

Benign

0.60

PhyloP100

-0.72

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over