rs4812987

Positions:

• chr20-46044606-T-C

Variant summary

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

The NM_020708.5(SLC12A5):​c.1395-360T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0348 in 152,234 control chromosomes in the GnomAD database, including 181 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 0.035 (181 hom., cov: 32)
• Consequence: SLC12A5 NM_020708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC12A5	NM_020708.5	c.1395-360T>C		intron_variant		ENST00000243964.7	NP_065759.1
SLC12A5	NM_001134771.2	c.1464-360T>C		intron_variant			NP_001128243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A5	ENST00000243964.7	c.1395-360T>C		intron_variant		1	NM_020708.5	ENSP00000243964	A1

Frequencies

GnomAD3 genomes AF: 0.0347 AC: 5282 AN: 152116 Hom.: 177 Cov.: 32

Gnomad AFR AF: 0.0187

Gnomad AMI AF: 0.0396

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0525

Gnomad EAS AF: 0.0323

Gnomad SAS AF: 0.0783

Gnomad FIN AF: 0.0251

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0246

Gnomad OTH AF: 0.0396

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

GnomAD4 genome AF: 0.0348 AC: 5292 AN: 152234 Hom.: 181 Cov.: 32 AF XY: 0.0371 AC XY: 2759 AN XY: 74438

Gnomad4 AFR AF: 0.0186

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.0525

Gnomad4 EAS AF: 0.0325

Gnomad4 SAS AF: 0.0775

Gnomad4 FIN AF: 0.0251

Gnomad4 NFE AF: 0.0246

Gnomad4 OTH AF: 0.0402

Alfa AF: 0.0280 Hom.: 14

Bravo AF: 0.0406

Asia WGS AF: 0.0530 AC: 185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.62

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: rs4812987; hg19: chr20-44673245;