Genetic Variant SLC6A1:c.-5G>A (chr3-11017207-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4BP6_Very_StrongBS2

The NM_003042.4(SLC6A1):c.-5G>A variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00028 in 1,613,450 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 1 hom. )

Consequence

SLC6A1
NM_003042.4 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.73

Publications

1 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 links:

SLC6A1-AS1 (HGNC:40546): (SLC6A1 antisense RNA 1)

SLC6A1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.15).

BP6

Variant 3-11017207-G-A is Benign according to our data. Variant chr3-11017207-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 546929.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 31 AD,Unknown gene.

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.-5G>A	5_prime_UTR	Exon 3 of 16	NP_003033.3
SLC6A1	NM_001348250.2		c.-5G>A	5_prime_UTR	Exon 3 of 16	NP_001335179.1	P30531
SLC6A1	NM_001348251.2		c.-175G>A	5_prime_UTR	Exon 3 of 16	NP_001335180.1	A0A2R8Y4I3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC6A1	ENST00000287766.10	TSL:1 MANE Select	c.-5G>A		5_prime_UTR	Exon 3 of 16	ENSP00000287766.4	P30531
SLC6A1	ENST00000698198.1		c.68G>A	p.Arg23Gln	missense	Exon 1 of 14	ENSP00000513602.1	A0A8V8TMZ9
SLC6A1	ENST00000644803.1		c.-5G>A		5_prime_UTR	Exon 1 of 14	ENSP00000494469.1	A0A2R8YDD5

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000208

AC:

AN:

250318

AF XY:

0.000192

show subpopulations

Gnomad AFR exome

AF:

0.0000621

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000425

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000288

AC:

421

AN:

1461224

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

195

AN XY:

726868

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33466

American (AMR)

AF:

0.000246

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53234

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.000354

AC:

394

AN:

1111684

Other (OTH)

AF:

0.000166

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000204

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41550

American (AMR)

AF:

0.000262

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000196

Hom.:

Bravo

AF:

0.000170

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000593

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Inborn genetic diseases (1)

SLC6A1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.15

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

3.7

PromoterAI

0.043

Neutral

(source)

Mutation Taster

=294/6

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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