rs9074

Positions:

• chr20-46060026-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_020708.5(SLC12A5):​c.*2421G>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.223 in 174,214 control chromosomes in the GnomAD database, including 5,084 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 0.21 (4157 hom., cov: 33)
  • Exomes 𝑓: 0.29 (927 hom.)
• Consequence: SLC12A5 NM_020708.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.76

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC12A5	NM_020708.5	c.*2421G>A		3_prime_UTR_variant	26/26	ENST00000243964.7
SLC12A5	NM_001134771.2	c.*2421G>A		3_prime_UTR_variant	26/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC12A5	ENST00000243964.7	c.*2421G>A		3_prime_UTR_variant	26/26	1	NM_020708.5	A1
SLC12A5	ENST00000616202.4	c.*1288G>A		3_prime_UTR_variant	7/7	1
SLC12A5	ENST00000626937.2	c.*394G>A		3_prime_UTR_variant	7/7	1
SLC12A5	ENST00000616933.4	c.*5090G>A		3_prime_UTR_variant	27/27	5

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32463 AN: 152046 Hom.: 4159 Cov.: 33

Gnomad AFR AF: 0.0664

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.289 AC: 6376 AN: 22050 Hom.: 927 Cov.: 0 AF XY: 0.294 AC XY: 3245 AN XY: 11054

Gnomad4 AFR exome AF: 0.0660

Gnomad4 AMR exome AF: 0.237

Gnomad4 ASJ exome AF: 0.311

Gnomad4 EAS exome AF: 0.321

Gnomad4 SAS exome AF: 0.210

Gnomad4 FIN exome AF: 0.311

Gnomad4 NFE exome AF: 0.296

Gnomad4 OTH exome AF: 0.303

GnomAD4 genome AF: 0.213 AC: 32452 AN: 152164 Hom.: 4157 Cov.: 33 AF XY: 0.218 AC XY: 16208 AN XY: 74368

Gnomad4 AFR AF: 0.0662

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.230

Alfa AF: 0.261 Hom.: 11076

Bravo AF: 0.201

Asia WGS AF: 0.245 AC: 851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	16
DANN	Benign	0.91

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: rs9074; hg19: chr20-44688665;