20-46022179-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0270

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]

ACMG classification

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/exons	MANE	UniProt
SLC12A5	NM_001134771.2	c.121+293A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC12A5	ENST00000413737.2	c.48+293A>G		intron_variant		3
SLC12A5	ENST00000454036.6	c.121+293A>G		intron_variant		5		P3
SLC12A5	ENST00000626701.1	c.121+293A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.490 AC: 72323 AN: 147582 Hom.: 18038 Cov.: 23

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

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.: 23 AF XY: 0.495 AC XY: 35559 AN XY: 71834

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

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

Other links and lift over

dbSNP: rs6130997; hg19: chr20-44650818;