rs2297200

chr20-46055887-T-Achr20-46055887-T-Cchr20-46055887-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020708.5(SLC12A5):c.2788-263T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 465,768 control chromosomes in the GnomAD database, including 27,173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (8006 hom., cov: 32)
  • Exomes 𝑓: 0.34 (19167 hom.)
• Consequence: SLC12A5 NM_020708.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.463

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 20-46055887-T-A is Benign according to our data. Variant chr20-46055887-T-A is described in ClinVar as [Benign]. Clinvar id is 1253299.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC12A5	NM_020708.5	c.2788-263T>A		intron_variant		ENST00000243964.7
SLC12A5	NM_001134771.2	c.2857-263T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC12A5	ENST00000243964.7	c.2788-263T>A		intron_variant		1	NM_020708.5	A1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48450 AN: 151872 Hom.: 7995 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.354

GnomAD4 exome AF: 0.342 AC: 107456 AN: 313776 Hom.: 19167 Cov.: 3 AF XY: 0.344 AC XY: 56967 AN XY: 165364

Gnomad4 AFR exome AF: 0.261

Gnomad4 AMR exome AF: 0.436

Gnomad4 ASJ exome AF: 0.327

Gnomad4 EAS exome AF: 0.476

Gnomad4 SAS exome AF: 0.370

Gnomad4 FIN exome AF: 0.281

Gnomad4 NFE exome AF: 0.329

Gnomad4 OTH exome AF: 0.336

GnomAD4 genome AF: 0.319 AC: 48477 AN: 151992 Hom.: 8006 Cov.: 32 AF XY: 0.318 AC XY: 23651 AN XY: 74298

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.325

Gnomad4 OTH AF: 0.357

Alfa AF: 0.179 Hom.: 360

Bravo AF: 0.331

Asia WGS AF: 0.462 AC: 1607 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.4
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: rs2297200; hg19: chr20-44684526;