Genetic Variant SLC12A4:c.1132+20G>A (chr16-67951803-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005072.5(SLC12A4):c.1132+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,592,484 control chromosomes in the GnomAD database, including 15,649 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 0.16 ( 2114 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13535 hom. )

Consequence

SLC12A4
NM_005072.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.431

Publications

34 publications found

Variant links:

Genes affected

SLC12A4 (HGNC:10913): (solute carrier family 12 member 4) This gene encodes a member of the SLC12A transporter family. The encoded protein mediates the coupled movement of potassium and chloride ions across the plasma membrane. This gene is expressed ubiquitously. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jan 2013]

SLC12A4 links:

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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=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005072.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC12A4	NM_005072.5	MANE Select	c.1132+20G>A	intron	N/A	NP_005063.1	Q9UP95-1
SLC12A4	NM_001145962.1		c.1138+20G>A	intron	N/A	NP_001139434.1	Q9UP95-7
SLC12A4	NM_001145961.2		c.1132+20G>A	intron	N/A	NP_001139433.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC12A4	ENST00000316341.8	TSL:1 MANE Select	c.1132+20G>A	intron	N/A	ENSP00000318557.3	Q9UP95-1
SLC12A4	ENST00000572010.6	TSL:1	n.1289+20G>A	intron	N/A
SLC12A4	ENST00000964383.1		c.1132+20G>A	intron	N/A	ENSP00000634442.1

Frequencies

GnomAD3 genomes

AF:

0.160

AC:

24400

AN:

152042

Hom.:

2115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.218

Gnomad AMR

AF:

0.152

Gnomad ASJ

AF:

0.164

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.189

Gnomad FIN

AF:

0.171

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.153

GnomAD2 exomes

AF:

0.154

AC:

34535

AN:

224102

AF XY:

0.152

show subpopulations

Gnomad AFR exome

AF:

0.228

Gnomad AMR exome

AF:

0.161

Gnomad ASJ exome

AF:

0.161

Gnomad EAS exome

AF:

0.112

Gnomad FIN exome

AF:

0.169

Gnomad NFE exome

AF:

0.132

Gnomad OTH exome

AF:

0.152

GnomAD4 exome

AF:

0.133

AC:

191822

AN:

1440324

Hom.:

13535

Cov.:

AF XY:

0.135

AC XY:

96515

AN XY:

715648

show subpopulations

African (AFR)

AF:

0.211

AC:

6997

AN:

33188

American (AMR)

AF:

0.164

AC:

6833

AN:

41580

Ashkenazi Jewish (ASJ)

AF:

0.162

AC:

4149

AN:

25662

East Asian (EAS)

AF:

0.125

AC:

4870

AN:

39042

South Asian (SAS)

AF:

0.192

AC:

16171

AN:

84374

European-Finnish (FIN)

AF:

0.163

AC:

8462

AN:

51818

Middle Eastern (MID)

AF:

0.120

AC:

609

AN:

5072

European-Non Finnish (NFE)

AF:

0.123

AC:

135834

AN:

1100032

Other (OTH)

AF:

0.133

AC:

7897

AN:

59556

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

8808

17615

26423

35230

44038

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5004

10008

15012

20016

25020

<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:

0.160

AC:

24410

AN:

152160

Hom.:

2114

Cov.:

AF XY:

0.163

AC XY:

12143

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.218

AC:

9057

AN:

41488

American (AMR)

AF:

0.152

AC:

2327

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.164

AC:

568

AN:

3468

East Asian (EAS)

AF:

0.103

AC:

534

AN:

5186

South Asian (SAS)

AF:

0.188

AC:

908

AN:

4822

European-Finnish (FIN)

AF:

0.171

AC:

1810

AN:

10590

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.127

AC:

8642

AN:

67998

Other (OTH)

AF:

0.157

AC:

331

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1048

2095

3143

4190

5238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

262

524

786

1048

1310

<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:

0.143

Hom.:

563

Bravo

AF:

0.161

Asia WGS

AF:

0.187

AC:

653

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.0

(source)

DANN

Benign

0.70

PhyloP100

0.43

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over