dbSNP rs16960682: SLC12A1:n.3140G>A (chr15-48227465-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000560692.5(SLC12A1):n.3140G>A 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 0.00136 in 375,844 control chromosomes in the GnomAD database, including 3 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 0.0028 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00036 ( 1 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).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00284 (433/152212) while in subpopulation AFR AF = 0.00999 (415/41538). AF 95% confidence interval is 0.0092. There are 2 homozygotes in GnomAd4. There are 195 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
SLC12A1	NM_000338.3 link	c.724+894G>A	intron_variant	Intron 5 of 26	ENST00000380993.8	NP_000329.2
LOC128966560	XR_932204.4 link	n.351C>T	non_coding_transcript_exon_variant	Exon 3 of 3
SLC12A1	NM_001184832.2 link	c.724+291G>A	intron_variant	Intron 5 of 26		NP_001171761.1
SLC12A1	NM_001384136.1 link	c.724+1518G>A	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>A		intron_variant	Intron 5 of 26	5	NM_000338.3	ENSP00000370381.3

Frequencies

GnomAD3 genomes

AF:

0.00282

AC:

429

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00992

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00192

GnomAD4 exome

AF:

0.000358

AC:

AN:

223632

Hom.:

Cov.:

AF XY:

0.000258

AC XY:

AN XY:

120252

show subpopulations

African (AFR)

AF:

0.00964

AC:

AN:

6330

American (AMR)

AF:

0.000298

AC:

AN:

10064

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6186

East Asian (EAS)

AF:

0.00

AC:

AN:

11274

South Asian (SAS)

AF:

0.0000303

AC:

AN:

32988

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10708

Middle Eastern (MID)

AF:

0.00

AC:

AN:

868

European-Non Finnish (NFE)

AF:

0.0000150

AC:

AN:

133234

Other (OTH)

AF:

0.00109

AC:

AN:

11980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.549

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00284

AC:

433

AN:

152212

Hom.:

Cov.:

AF XY:

0.00262

AC XY:

195

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.00999

AC:

415

AN:

41538

American (AMR)

AF:

0.000850

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68026

Other (OTH)

AF:

0.00190

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.00329

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.59

(source)

DANN

Benign

0.63

PhyloP100

-0.72

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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