dbSNP rs3848723: SLC12A5:c.280-106A>G (chr20-46035671-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_020708.5(SLC12A5):c.280-106A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0275 in 1,516,658 control chromosomes in the GnomAD database, including 1,057 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 0.029 ( 173 hom., cov: 32)

Exomes 𝑓: 0.027 ( 884 hom. )

Consequence

SLC12A5
NM_020708.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0420

Publications

4 publications found

Variant links:

Genes affected

SLC12A5 (HGNC:13818): (solute carrier family 12 member 5) K-Cl cotransporters are proteins that lower intracellular chloride concentrations below the electrochemical equilibrium potential. The protein encoded by this gene is an integral membrane K-Cl cotransporter that can function in either a net efflux or influx pathway, depending on the chemical concentration gradients of potassium and chloride. The encoded protein can act as a homomultimer, or as a heteromultimer with other K-Cl cotransporters, to maintain chloride homeostasis in neurons. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Sep 2008]

SLC12A5 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 34
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics
epilepsy of infancy with migrating focal seizures
Inheritance: AR Classification: STRONG Submitted by: G2P
malignant migrating partial seizures of infancy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
epilepsy, idiopathic generalized, susceptibility to, 14
Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Illumina, Ambry Genetics
genetic developmental and epileptic encephalopathy
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

SLC12A5 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=-0.92).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A5	NM_020708.5 link	c.280-106A>G		intron_variant	Intron 3 of 25	ENST00000243964.7	NP_065759.1
SLC12A5	NM_001134771.2 link	c.349-106A>G		intron_variant	Intron 3 of 25		NP_001128243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A5	ENST00000243964.7 link	c.280-106A>G		intron_variant	Intron 3 of 25	1	NM_020708.5	ENSP00000243964.4

Frequencies

GnomAD3 genomes

AF:

0.0293

AC:

4457

AN:

151970

Hom.:

170

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00805

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.0539

Gnomad EAS

AF:

0.0285

Gnomad SAS

AF:

0.0388

Gnomad FIN

AF:

0.0182

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0224

Gnomad OTH

AF:

0.0335

GnomAD4 exome

AF:

0.0273

AC:

37295

AN:

1364570

Hom.:

884

Cov.:

AF XY:

0.0276

AC XY:

18476

AN XY:

669826

show subpopulations

African (AFR)

AF:

0.00513

AC:

161

AN:

31388

American (AMR)

AF:

0.148

AC:

5127

AN:

34620

Ashkenazi Jewish (ASJ)

AF:

0.0527

AC:

1138

AN:

21588

East Asian (EAS)

AF:

0.0360

AC:

1372

AN:

38094

South Asian (SAS)

AF:

0.0420

AC:

3080

AN:

73398

European-Finnish (FIN)

AF:

0.0184

AC:

847

AN:

46058

Middle Eastern (MID)

AF:

0.0168

AC:

AN:

4406

European-Non Finnish (NFE)

AF:

0.0225

AC:

23778

AN:

1058470

Other (OTH)

AF:

0.0304

AC:

1718

AN:

56548

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1787

3574

5361

7148

8935

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1024

2048

3072

4096

5120

<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:

0.0293

AC:

4461

AN:

152088

Hom.:

173

Cov.:

AF XY:

0.0312

AC XY:

2323

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.00803

AC:

333

AN:

41482

American (AMR)

AF:

0.117

AC:

1787

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0539

AC:

187

AN:

3470

East Asian (EAS)

AF:

0.0284

AC:

147

AN:

5174

South Asian (SAS)

AF:

0.0388

AC:

187

AN:

4818

European-Finnish (FIN)

AF:

0.0182

AC:

192

AN:

10578

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0223

AC:

1519

AN:

67966

Other (OTH)

AF:

0.0336

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

208

417

625

834

1042

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<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:

0.0231

Hom.:

Bravo

AF:

0.0348

Asia WGS

AF:

0.0320

AC:

111

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

3.6

(source)

DANN

Benign

0.52

PhyloP100

-0.042

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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