20-46035671-A-G

Position:

• chr20-46035671-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.280-106A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0275 in 1,516,658 control chromosomes in the GnomAD database, including 1,057 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 0.029 (173 hom., cov: 32)
  • Exomes 𝑓: 0.027 (884 hom.)
• Consequence: SLC12A5 NM_020708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420

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 = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC12A5	NM_020708.5	c.280-106A>G		intron_variant		ENST00000243964.7
SLC12A5	NM_001134771.2	c.349-106A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC12A5	ENST00000243964.7	c.280-106A>G		intron_variant		1	NM_020708.5	A1

Frequencies

GnomAD3 genomes AF: 0.0293 AC: 4457 AN: 151970 Hom.: 170 Cov.: 32

Gnomad AFR AF: 0.00805

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0539

Gnomad EAS AF: 0.0285

Gnomad SAS AF: 0.0388

Gnomad FIN AF: 0.0182

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0224

Gnomad OTH AF: 0.0335

GnomAD4 exome AF: 0.0273 AC: 37295 AN: 1364570 Hom.: 884 Cov.: 26 AF XY: 0.0276 AC XY: 18476 AN XY: 669826

Gnomad4 AFR exome AF: 0.00513

Gnomad4 AMR exome AF: 0.148

Gnomad4 ASJ exome AF: 0.0527

Gnomad4 EAS exome AF: 0.0360

Gnomad4 SAS exome AF: 0.0420

Gnomad4 FIN exome AF: 0.0184

Gnomad4 NFE exome AF: 0.0225

Gnomad4 OTH exome AF: 0.0304

GnomAD4 genome AF: 0.0293 AC: 4461 AN: 152088 Hom.: 173 Cov.: 32 AF XY: 0.0312 AC XY: 2323 AN XY: 74366

Gnomad4 AFR AF: 0.00803

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.0539

Gnomad4 EAS AF: 0.0284

Gnomad4 SAS AF: 0.0388

Gnomad4 FIN AF: 0.0182

Gnomad4 NFE AF: 0.0223

Gnomad4 OTH AF: 0.0336

Alfa AF: 0.0231 Hom.: 11

Bravo AF: 0.0348

Asia WGS AF: 0.0320 AC: 111 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	3.6
DANN	Benign	0.52

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: rs3848723; hg19: chr20-44664310;