rs148429200
Positions:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_003042.4(SLC6A1):c.411C>T(p.Asn137=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000916 in 1,613,836 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0012 ( 2 hom., cov: 33)
Exomes 𝑓: 0.00088 ( 9 hom. )
Consequence
SLC6A1
NM_003042.4 synonymous
NM_003042.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.150
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 -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
?
Variant 3-11018638-C-T is Benign according to our data. Variant chr3-11018638-C-T is described in ClinVar as [Benign]. Clinvar id is 475480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.15 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00125 (190/152330) while in subpopulation EAS AF= 0.0129 (67/5184). AF 95% confidence interval is 0.0104. There are 2 homozygotes in gnomad4. There are 110 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 190 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC6A1 | NM_003042.4 | c.411C>T | p.Asn137= | synonymous_variant | 5/16 | ENST00000287766.10 | |
SLC6A1-AS1 | NR_046647.1 | n.105+482G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC6A1 | ENST00000287766.10 | c.411C>T | p.Asn137= | synonymous_variant | 5/16 | 1 | NM_003042.4 | P1 | |
SLC6A1-AS1 | ENST00000414969.2 | n.105+482G>A | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.00124 AC: 188AN: 152212Hom.: 2 Cov.: 33
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GnomAD3 exomes AF: 0.00250 AC: 629AN: 251416Hom.: 5 AF XY: 0.00219 AC XY: 298AN XY: 135888
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GnomAD4 exome AF: 0.000881 AC: 1288AN: 1461506Hom.: 9 Cov.: 30 AF XY: 0.000827 AC XY: 601AN XY: 727096
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GnomAD4 genome ? AF: 0.00125 AC: 190AN: 152330Hom.: 2 Cov.: 33 AF XY: 0.00148 AC XY: 110AN XY: 74482
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2023 | SLC6A1: BP4, BP7, BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 03, 2020 | - - |
SLC6A1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 18, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 16, 2016 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Myoclonic-atonic epilepsy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
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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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at