dbSNP rs1919075: SLC6A1:c.-216+8404G>A (chr3-11001333-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.-216+8404G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,216 control chromosomes in the GnomAD database, including 5,971 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 0.25 ( 5967 hom., cov: 32)

Exomes 𝑓: 0.26 ( 4 hom. )

Consequence

SLC6A1
NM_003042.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.361

Publications

6 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=-0.82).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.415 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.-216+8404G>A	intron	N/A	NP_003033.3
SLC6A1	NM_001348250.2		c.-155+8404G>A	intron	N/A	NP_001335179.1	P30531
SLC6A1	NM_001348251.2		c.-325+8404G>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.-216+8404G>A	intron	N/A	ENSP00000287766.4	P30531
SLC6A1	ENST00000642201.1		c.-26+8404G>A	intron	N/A	ENSP00000494778.1	P30531
SLC6A1	ENST00000642515.1		c.-1223+8404G>A	intron	N/A	ENSP00000496348.1	P30531

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

38046

AN:

151990

Hom.:

5961

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0698

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.423

Gnomad ASJ

AF:

0.282

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.289

Gnomad FIN

AF:

0.310

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.269

GnomAD4 exome

AF:

0.259

AC:

AN:

108

Hom.:

Cov.:

AF XY:

0.329

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.192

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.306

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

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:

0.250

AC:

38059

AN:

152108

Hom.:

5967

Cov.:

AF XY:

0.253

AC XY:

18776

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.0697

AC:

2892

AN:

41518

American (AMR)

AF:

0.423

AC:

6468

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.282

AC:

978

AN:

3468

East Asian (EAS)

AF:

0.193

AC:

996

AN:

5168

South Asian (SAS)

AF:

0.289

AC:

1391

AN:

4806

European-Finnish (FIN)

AF:

0.310

AC:

3288

AN:

10592

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.311

AC:

21166

AN:

67974

Other (OTH)

AF:

0.272

AC:

572

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1348

2696

4044

5392

6740

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

388

776

1164

1552

1940

<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:

0.302

Hom.:

3443

Bravo

AF:

0.253

Asia WGS

AF:

0.235

AC:

818

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.1

(source)

DANN

Benign

0.69

PhyloP100

0.36

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