rs6130998

Positions:

• chr20-46024480-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+2594C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,166 control chromosomes in the GnomAD database, including 2,714 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 0.18 (2714 hom., cov: 33)
• Consequence: SLC12A5 NM_001134771.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.191

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=-0.48).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC12A5	NM_001134771.2	c.121+2594C>T		intron_variant			NP_001128243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A5	ENST00000454036.6	c.121+2594C>T		intron_variant		5		ENSP00000387694	P3
SLC12A5	ENST00000428198.1	n.111+2594C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26845 AN: 152048 Hom.: 2711 Cov.: 33

Gnomad AFR AF: 0.0868

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.176 AC: 26852 AN: 152166 Hom.: 2714 Cov.: 33 AF XY: 0.180 AC XY: 13419 AN XY: 74408

Gnomad4 AFR AF: 0.0870

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.173

Alfa AF: 0.190 Hom.: 376

Bravo AF: 0.169

Asia WGS AF: 0.235 AC: 816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	7.1
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6130998; hg19: chr20-44653119; COSMIC: COSV54797275; COSMIC: COSV54797275;