rs16991026

Positions:

• chr20-46051200-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020708.5(SLC12A5):​c.2182-475A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0273 in 152,308 control chromosomes in the GnomAD database, including 150 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 0.027 (150 hom., cov: 32)
• Consequence: SLC12A5 NM_020708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC12A5	NM_020708.5	c.2182-475A>G		intron_variant		ENST00000243964.7
SLC12A5	NM_001134771.2	c.2251-475A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC12A5	ENST00000243964.7	c.2182-475A>G		intron_variant		1	NM_020708.5	A1

Frequencies

GnomAD3 genomes AF: 0.0273 AC: 4157 AN: 152190 Hom.: 148 Cov.: 32

Gnomad AFR AF: 0.00738

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0519

Gnomad EAS AF: 0.00559

Gnomad SAS AF: 0.0259

Gnomad FIN AF: 0.0193

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0230

Gnomad OTH AF: 0.0330

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0273 AC: 4163 AN: 152308 Hom.: 150 Cov.: 32 AF XY: 0.0289 AC XY: 2152 AN XY: 74472

Gnomad4 AFR AF: 0.00736

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.0519

Gnomad4 EAS AF: 0.00560

Gnomad4 SAS AF: 0.0257

Gnomad4 FIN AF: 0.0193

Gnomad4 NFE AF: 0.0230

Gnomad4 OTH AF: 0.0336

Alfa AF: 0.0284 Hom.: 24

Bravo AF: 0.0315

Asia WGS AF: 0.0200 AC: 68 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.44
DANN	Benign	0.44

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

LitVar

Other links and lift over

dbSNP: rs16991026; hg19: chr20-44679839;