Genetic Variant SLC12A5:c.121+293A>G (chr20-46022179-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001134771.2(SLC12A5):c.121+293A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 266,798 control chromosomes in the GnomAD database, including 30,219 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.49 ( 18050 hom., cov: 23)

Exomes 𝑓: 0.42 ( 12169 hom. )

Consequence

SLC12A5
NM_001134771.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0270

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 links:

SLC12A5-AS1 (HGNC:53143): (SLC12A5 and MMP9 antisense RNA 1)

SLC12A5-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 20-46022179-A-G is Benign according to our data. Variant chr20-46022179-A-G is described in ClinVar as [Benign]. Clinvar id is 1183011.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A5	NM_001134771.2 link	c.121+293A>G		intron_variant	Intron 1 of 25		NP_001128243.1	Q9H2X9-1
SLC12A5-AS1	NR_147699.1 link	n.-106T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
SLC12A5	ENST00000454036.6 link	c.121+293A>G	intron_variant	Intron 1 of 25	5	ENSP00000387694.1	Q9H2X9-1
SLC12A5	ENST00000626701.1 link	c.121+293A>G	intron_variant	Intron 1 of 2	3	ENSP00000487372.1	A0A0D9SGD0
SLC12A5	ENST00000413737.2 link	c.46+293A>G	intron_variant	Intron 1 of 2	3	ENSP00000487291.1	A0A0D9SGA5

Frequencies

GnomAD3 genomes

AF:

0.490

AC:

72323

AN:

147582

Hom.:

18038

Cov.:

show subpopulations

Gnomad AFR

AF:

0.553

Gnomad AMI

AF:

0.547

Gnomad AMR

AF:

0.441

Gnomad ASJ

AF:

0.455

Gnomad EAS

AF:

0.763

Gnomad SAS

AF:

0.597

Gnomad FIN

AF:

0.457

Gnomad MID

AF:

0.397

Gnomad NFE

AF:

0.444

Gnomad OTH

AF:

0.449

GnomAD4 exome

AF:

0.421

AC:

50116

AN:

119098

Hom.:

12169

AF XY:

0.423

AC XY:

26104

AN XY:

61762

show subpopulations

Gnomad4 AFR exome

AF:

0.507

Gnomad4 AMR exome

AF:

0.386

Gnomad4 ASJ exome

AF:

0.413

Gnomad4 EAS exome

AF:

0.710

Gnomad4 SAS exome

AF:

0.495

Gnomad4 FIN exome

AF:

0.384

Gnomad4 NFE exome

AF:

0.386

Gnomad4 OTH exome

AF:

0.418

GnomAD4 genome

AF:

0.490

AC:

72375

AN:

147700

Hom.:

18050

Cov.:

AF XY:

0.495

AC XY:

35559

AN XY:

71834

show subpopulations

Gnomad4 AFR

AF:

0.553

Gnomad4 AMR

AF:

0.441

Gnomad4 ASJ

AF:

0.455

Gnomad4 EAS

AF:

0.762

Gnomad4 SAS

AF:

0.596

Gnomad4 FIN

AF:

0.457

Gnomad4 NFE

AF:

0.444

Gnomad4 OTH

AF:

0.450

Alfa

AF:

0.351

Hom.:

951

Bravo

AF:

0.493

Asia WGS

AF:

0.598

AC:

2072

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

6.2

DANN

Benign

0.52

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over