rs41282782
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The ENST00000243964.7(SLC12A5):c.1512G>A(p.Thr504=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0461 in 1,612,380 control chromosomes in the GnomAD database, including 1,971 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.048 ( 209 hom., cov: 32)
Exomes 𝑓: 0.046 ( 1762 hom. )
Consequence
SLC12A5
ENST00000243964.7 synonymous
ENST00000243964.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.24
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
Variant 20-46045083-G-A is Benign according to our data. Variant chr20-46045083-G-A is described in ClinVar as [Benign]. Clinvar id is 475642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-2.24 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0483 (7357/152304) while in subpopulation NFE AF= 0.0495 (3365/68020). AF 95% confidence interval is 0.0481. There are 209 homozygotes in gnomad4. There are 3684 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 209 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC12A5 | NM_020708.5 | c.1512G>A | p.Thr504= | synonymous_variant | 12/26 | ENST00000243964.7 | NP_065759.1 | |
SLC12A5 | NM_001134771.2 | c.1581G>A | p.Thr527= | synonymous_variant | 12/26 | NP_001128243.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC12A5 | ENST00000243964.7 | c.1512G>A | p.Thr504= | synonymous_variant | 12/26 | 1 | NM_020708.5 | ENSP00000243964 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0483 AC: 7357AN: 152186Hom.: 209 Cov.: 32
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GnomAD3 exomes AF: 0.0398 AC: 9925AN: 249152Hom.: 270 AF XY: 0.0393 AC XY: 5298AN XY: 134656
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GnomAD4 exome AF: 0.0459 AC: 66997AN: 1460076Hom.: 1762 Cov.: 31 AF XY: 0.0445 AC XY: 32354AN XY: 726302
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GnomAD4 genome AF: 0.0483 AC: 7357AN: 152304Hom.: 209 Cov.: 32 AF XY: 0.0495 AC XY: 3684AN XY: 74486
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 34 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at