20-46037956-G-T

Position:

• chr20-46037956-G-T

Variant summary

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

The NM_020708.5(SLC12A5):​c.612+571G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,040 control chromosomes in the GnomAD database, including 6,857 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 0.27 (6857 hom., cov: 31)
• Consequence: SLC12A5 NM_020708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08

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]

SLC12A5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) 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_020708.5	c.612+571G>T		intron_variant		ENST00000243964.7	NP_065759.1
SLC12A5	NM_001134771.2	c.681+571G>T		intron_variant			NP_001128243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A5	ENST00000243964.7	c.612+571G>T		intron_variant		1	NM_020708.5	ENSP00000243964.4

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41366 AN: 151922 Hom.: 6863 Cov.: 31

Gnomad AFR AF: 0.0818

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.272 AC: 41353 AN: 152040 Hom.: 6857 Cov.: 31 AF XY: 0.271 AC XY: 20155 AN XY: 74310

Gnomad4 AFR AF: 0.0815

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.295

Alfa AF: 0.355 Hom.: 20587

Bravo AF: 0.257

Asia WGS AF: 0.194 AC: 678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.1
DANN	Benign	0.75

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: rs3848726; hg19: chr20-44666595;