chr15-48231070-A-G

Variant summary

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

The NM_000338.3(SLC12A1):​c.975+567A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 152,136 control chromosomes in the GnomAD database, including 33,991 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 0.63 ( 33991 hom., cov: 32)

Consequence

SLC12A1
NM_000338.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.09

Publications

9 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

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=-0.91).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC12A1NM_000338.3 linkc.975+567A>G intron_variant Intron 7 of 26 ENST00000380993.8 NP_000329.2 Q13621-1Q8IUN5
SLC12A1NM_001184832.2 linkc.975+567A>G intron_variant Intron 7 of 26 NP_001171761.1 Q13621-3B4DPF4
SLC12A1NM_001384136.1 linkc.975+567A>G intron_variant Intron 7 of 26 NP_001371065.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC12A1ENST00000380993.8 linkc.975+567A>G intron_variant Intron 7 of 26 5 NM_000338.3 ENSP00000370381.3 Q13621-1

Frequencies

GnomAD3 genomes
AF:
0.626
AC:
95213
AN:
152016
Hom.:
34006
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.280
Gnomad AMI
AF:
0.831
Gnomad AMR
AF:
0.681
Gnomad ASJ
AF:
0.775
Gnomad EAS
AF:
0.332
Gnomad SAS
AF:
0.743
Gnomad FIN
AF:
0.794
Gnomad MID
AF:
0.797
Gnomad NFE
AF:
0.800
Gnomad OTH
AF:
0.666
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.626
AC:
95208
AN:
152136
Hom.:
33991
Cov.:
32
AF XY:
0.629
AC XY:
46756
AN XY:
74356
show subpopulations
African (AFR)
AF:
0.280
AC:
11611
AN:
41488
American (AMR)
AF:
0.680
AC:
10389
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
0.775
AC:
2690
AN:
3472
East Asian (EAS)
AF:
0.331
AC:
1714
AN:
5178
South Asian (SAS)
AF:
0.743
AC:
3579
AN:
4814
European-Finnish (FIN)
AF:
0.794
AC:
8401
AN:
10576
Middle Eastern (MID)
AF:
0.796
AC:
234
AN:
294
European-Non Finnish (NFE)
AF:
0.800
AC:
54438
AN:
68006
Other (OTH)
AF:
0.659
AC:
1394
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1414
2828
4243
5657
7071
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
748
1496
2244
2992
3740
<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:
0.740
Hom.:
54226
Bravo
AF:
0.602
Asia WGS
AF:
0.527
AC:
1836
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.047
DANN
Benign
0.29
PhyloP100
-2.1
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs12904216; hg19: chr15-48523267; API