rs11908352

chr20-46027501-C-Achr20-46027501-C-T

Variant summary

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

The NM_001134771.2(SLC12A5):c.121+5615C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,036 control chromosomes in the GnomAD database, including 2,944 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 0.19 (2944 hom., cov: 33)
• Consequence: SLC12A5 NM_001134771.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.187

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=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC12A5	NM_001134771.2	c.121+5615C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC12A5	ENST00000454036.6	c.121+5615C>A		intron_variant		5		P3
SLC12A5	ENST00000428198.1	n.112-162C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29576 AN: 151918 Hom.: 2946 Cov.: 33

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.195 AC: 29592 AN: 152036 Hom.: 2944 Cov.: 33 AF XY: 0.195 AC XY: 14455 AN XY: 74310

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.184

Alfa AF: 0.111 Hom.: 193

Bravo AF: 0.185

Asia WGS AF: 0.216 AC: 749 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	13
Dann	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11908352; hg19: chr20-44656140;