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, Illumina, G2P, Labcorp Genetics (formerly Invitae)
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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A1	NM_003042.4 link	c.582-477G>A		intron_variant	Intron 6 of 15	ENST00000287766.10	NP_003033.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A1	ENST00000287766.10 link	c.582-477G>A		intron_variant	Intron 6 of 15	1	NM_003042.4	ENSP00000287766.4

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over