20-46022971-GGAGGAAGAGGAGGAGGAGGAA-G

Position:

• chr20-46022971-GGAGGAAGAGGAGGAGGAGGAA-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BS1 BS2

The ENST00000626701.1(SLC12A5):​c.256_276del​(p.Arg86_Gly92del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00808 in 370,696 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0064 (3 hom., cov: 19)
  • Exomes 𝑓: 0.0091 (7 hom.)
• Consequence: SLC12A5 ENST00000626701.1 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.90

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 -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in ENST00000626701.1
• BP6: Variant 20-46022971-GGAGGAAGAGGAGGAGGAGGAA-G is Benign according to our data. Variant chr20-46022971-GGAGGAAGAGGAGGAGGAGGAA-G is described in ClinVar as [Benign]. Clinvar id is 1686325.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00643 (900/139924) while in subpopulation NFE AF= 0.00962 (614/63818). AF 95% confidence interval is 0.00899. There are 3 homozygotes in gnomad4. There are 432 alleles in male gnomad4 subpopulation. Median coverage is 19. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC12A5	NM_001134771.2	c.121+1091_121+1111del		intron_variant			NP_001128243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A5	ENST00000413737.2	c.96_116del	p.Arg33_Gly39del	inframe_deletion	2/3	3		ENSP00000487291
SLC12A5	ENST00000626701.1	c.256_276del	p.Arg86_Gly92del	inframe_deletion	2/3	3		ENSP00000487372
SLC12A5	ENST00000454036.6	c.121+1091_121+1111del		intron_variant		5		ENSP00000387694	P3

Frequencies

GnomAD3 genomes AF: 0.00644 AC: 900 AN: 139858 Hom.: 3 Cov.: 19

Gnomad AFR AF: 0.00215

Gnomad AMI AF: 0.0477

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.00120

Gnomad SAS AF: 0.00464

Gnomad FIN AF: 0.00201

Gnomad MID AF: 0.00338

Gnomad NFE AF: 0.00964

Gnomad OTH AF: 0.00835

GnomAD4 exome AF: 0.00908 AC: 2095 AN: 230772 Hom.: 7 AF XY: 0.00912 AC XY: 1092 AN XY: 119762

Gnomad4 AFR exome AF: 0.00302

Gnomad4 AMR exome AF: 0.00696

Gnomad4 ASJ exome AF: 0.0124

Gnomad4 EAS exome AF: 0.000512

Gnomad4 SAS exome AF: 0.00395

Gnomad4 FIN exome AF: 0.00250

Gnomad4 NFE exome AF: 0.0110

Gnomad4 OTH exome AF: 0.0105

GnomAD4 genome AF: 0.00643 AC: 900 AN: 139924 Hom.: 3 Cov.: 19 AF XY: 0.00636 AC XY: 432 AN XY: 67930

Gnomad4 AFR AF: 0.00214

Gnomad4 AMR AF: 0.00530

Gnomad4 ASJ AF: 0.00950

Gnomad4 EAS AF: 0.000959

Gnomad4 SAS AF: 0.00489

Gnomad4 FIN AF: 0.00201

Gnomad4 NFE AF: 0.00962

Gnomad4 OTH AF: 0.00884

Alfa AF: 0.00379 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs879435751; hg19: chr20-44651610;