rs142579600
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_003042.4(SLC6A1):c.471+6T>C variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00029 in 1,557,944 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0015 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00016 ( 0 hom. )
Consequence
SLC6A1
NM_003042.4 splice_donor_region, intron
NM_003042.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.006254
2
Clinical Significance
Conservation
PhyloP100: 0.979
Genes affected
SLC6A1 (HGNC:11042): (solute carrier family 6 member 1) The protein encoded by this gene is a gamma-aminobutyric acid (GABA) transporter that localizes to the plasma membrane. The encoded protein removes GABA from the synaptic cleft, restoring it to presynaptic terminals. [provided by RefSeq, Jan 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -18 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
Variant 3-11018704-T-C is Benign according to our data. Variant chr3-11018704-T-C is described in ClinVar as [Benign]. Clinvar id is 475482.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00146 (222/152090) while in subpopulation AFR AF= 0.00528 (219/41474). AF 95% confidence interval is 0.00471. There are 1 homozygotes in gnomad4. There are 114 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 222 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC6A1 | NM_003042.4 | c.471+6T>C | splice_donor_region_variant, intron_variant | ENST00000287766.10 | |||
SLC6A1-AS1 | NR_046647.1 | n.105+416A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC6A1 | ENST00000287766.10 | c.471+6T>C | splice_donor_region_variant, intron_variant | 1 | NM_003042.4 | P1 | |||
SLC6A1-AS1 | ENST00000414969.2 | n.105+416A>G | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.00143 AC: 217AN: 151972Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.000383 AC: 96AN: 250960Hom.: 0 AF XY: 0.000214 AC XY: 29AN XY: 135706
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GnomAD4 exome AF: 0.000164 AC: 230AN: 1405854Hom.: 0 Cov.: 24 AF XY: 0.000131 AC XY: 92AN XY: 702882
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GnomAD4 genome AF: 0.00146 AC: 222AN: 152090Hom.: 1 Cov.: 33 AF XY: 0.00153 AC XY: 114AN XY: 74352
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Myoclonic-atonic epilepsy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 25, 2019 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at