Genetic Variant SLC6A1:c.-204G>A (chr3-11015683-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003042.4(SLC6A1):c.-204G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 152,160 control chromosomes in the GnomAD database, including 17,991 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 17973 hom., cov: 33)

Exomes 𝑓: 0.57 ( 18 hom. )

Consequence

SLC6A1
NM_003042.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.451

Publications

4 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 3-11015683-G-A is Benign according to our data. Variant chr3-11015683-G-A is described in ClinVar as [Benign]. Clinvar id is 1246526.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A1	NM_003042.4 link	c.-204G>A		5_prime_UTR_variant	Exon 2 of 16	ENST00000287766.10	NP_003033.3	A0A024R2K8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A1	ENST00000287766.10 link	c.-204G>A		5_prime_UTR_variant	Exon 2 of 16	1	NM_003042.4	ENSP00000287766.4		P30531

Frequencies

GnomAD3 genomes

AF:

0.468

AC:

71136

AN:

151920

Hom.:

17960

Cov.:

show subpopulations

Gnomad AFR

AF:

0.279

Gnomad AMI

AF:

0.505

Gnomad AMR

AF:

0.577

Gnomad ASJ

AF:

0.446

Gnomad EAS

AF:

0.396

Gnomad SAS

AF:

0.388

Gnomad FIN

AF:

0.594

Gnomad MID

AF:

0.472

Gnomad NFE

AF:

0.551

Gnomad OTH

AF:

0.472

GnomAD4 exome

AF:

0.566

AC:

AN:

122

Hom.:

Cov.:

AF XY:

0.598

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.538

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.525

AC:

AN:

Other (OTH)

AF:

0.813

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.468

AC:

71177

AN:

152038

Hom.:

17973

Cov.:

AF XY:

0.469

AC XY:

34828

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.279

AC:

11571

AN:

41470

American (AMR)

AF:

0.577

AC:

8825

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.446

AC:

1547

AN:

3468

East Asian (EAS)

AF:

0.397

AC:

2040

AN:

5142

South Asian (SAS)

AF:

0.386

AC:

1863

AN:

4822

European-Finnish (FIN)

AF:

0.594

AC:

6271

AN:

10560

Middle Eastern (MID)

AF:

0.466

AC:

137

AN:

294

European-Non Finnish (NFE)

AF:

0.551

AC:

37454

AN:

67966

Other (OTH)

AF:

0.478

AC:

1008

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1849

3697

5546

7394

9243

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.460

Hom.:

9201

Bravo

AF:

0.459

Asia WGS

AF:

0.402

AC:

1400

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 19, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.0

(source)

DANN

Benign

0.79

PhyloP100

0.45

PromoterAI

0.0084

Neutral

(source)

Mutation Taster

=300/0

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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3-11015683-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over