dbSNP rs11712912: SLC6A1:c.582-477G>A (chr3-11021859-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003042.4(SLC6A1):c.582-477G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0907 in 154,990 control chromosomes in the GnomAD database, including 722 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.091 ( 707 hom., cov: 33)

Exomes 𝑓: 0.081 ( 15 hom. )

Consequence

SLC6A1
NM_003042.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.24

Publications

3 publications found

Variant links:

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]

SLC6A1 Gene-Disease associations (from GenCC):

epilepsy with myoclonic atonic seizures
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, Illumina, G2P
myoclonic-astatic epilepsy
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

SLC6A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003042.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC6A1	NM_003042.4	MANE Select	c.582-477G>A	intron	N/A	NP_003033.3
SLC6A1	NM_001348250.2		c.582-477G>A	intron	N/A	NP_001335179.1	P30531
SLC6A1	NM_001348251.2		c.222-477G>A	intron	N/A	NP_001335180.1	A0A2R8Y4I3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC6A1	ENST00000287766.10	TSL:1 MANE Select	c.582-477G>A	intron	N/A	ENSP00000287766.4	P30531
SLC6A1	ENST00000698198.1		c.654-477G>A	intron	N/A	ENSP00000513602.1	A0A8V8TMZ9
SLC6A1	ENST00000644803.1		c.582-477G>A	intron	N/A	ENSP00000494469.1	A0A2R8YDD5

Frequencies

GnomAD3 genomes

AF:

0.0909

AC:

13834

AN:

152166

Hom.:

703

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0892

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.0704

Gnomad ASJ

AF:

0.134

Gnomad EAS

AF:

0.0999

Gnomad SAS

AF:

0.121

Gnomad FIN

AF:

0.0448

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0987

Gnomad OTH

AF:

0.108

GnomAD4 exome

AF:

0.0813

AC:

220

AN:

2706

Hom.:

Cov.:

AF XY:

0.0688

AC XY:

108

AN XY:

1570

show subpopulations

African (AFR)

AF:

0.0909

AC:

AN:

American (AMR)

AF:

0.0278

AC:

AN:

144

Ashkenazi Jewish (ASJ)

AF:

0.119

AC:

AN:

East Asian (EAS)

AF:

0.0278

AC:

AN:

South Asian (SAS)

AF:

0.0645

AC:

AN:

186

European-Finnish (FIN)

AF:

0.0789

AC:

AN:

190

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0843

AC:

160

AN:

1898

Other (OTH)

AF:

0.0959

AC:

AN:

146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0909

AC:

13841

AN:

152284

Hom.:

707

Cov.:

AF XY:

0.0891

AC XY:

6633

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0892

AC:

3705

AN:

41558

American (AMR)

AF:

0.0703

AC:

1075

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.134

AC:

465

AN:

3470

East Asian (EAS)

AF:

0.0996

AC:

515

AN:

5172

South Asian (SAS)

AF:

0.121

AC:

584

AN:

4828

European-Finnish (FIN)

AF:

0.0448

AC:

476

AN:

10620

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0988

AC:

6719

AN:

68016

Other (OTH)

AF:

0.109

AC:

230

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

641

1282

1922

2563

3204

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

158

316

474

632

790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0994

Hom.:

980

Bravo

AF:

0.0922

Asia WGS

AF:

0.109

AC:

380

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.82

(source)

DANN

Benign

0.33

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over