Genetic Variant SLC6A1:c.-153-65G>C (chr3-11016994-G-C) – 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.-153-65G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0558 in 569,292 control chromosomes in the GnomAD database, including 2,978 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1936 hom., cov: 32)

Exomes 𝑓: 0.038 ( 1042 hom. )

Consequence

SLC6A1
NM_003042.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0270

Publications

2 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=-0.84).

BP6

Variant 3-11016994-G-C is Benign according to our data. Variant chr3-11016994-G-C is described in ClinVar as [Benign]. Clinvar id is 1272282.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A1	NM_003042.4 link	c.-153-65G>C		intron_variant	Intron 2 of 15	ENST00000287766.10	NP_003033.3	A0A024R2K8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A1	ENST00000287766.10 link	c.-153-65G>C		intron_variant	Intron 2 of 15	1	NM_003042.4	ENSP00000287766.4		P30531

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15692

AN:

151896

Hom.:

1929

Cov.:

show subpopulations

Gnomad AFR

AF:

0.297

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.0699

Gnomad ASJ

AF:

0.0444

Gnomad EAS

AF:

0.0897

Gnomad SAS

AF:

0.0496

Gnomad FIN

AF:

0.0135

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0158

Gnomad OTH

AF:

0.0826

GnomAD4 exome

AF:

0.0384

AC:

16010

AN:

417280

Hom.:

1042

AF XY:

0.0375

AC XY:

8226

AN XY:

219100

show subpopulations

African (AFR)

AF:

0.303

AC:

3548

AN:

11698

American (AMR)

AF:

0.0500

AC:

874

AN:

17466

Ashkenazi Jewish (ASJ)

AF:

0.0454

AC:

590

AN:

12988

East Asian (EAS)

AF:

0.118

AC:

3354

AN:

28524

South Asian (SAS)

AF:

0.0441

AC:

1943

AN:

44092

European-Finnish (FIN)

AF:

0.00941

AC:

251

AN:

26680

Middle Eastern (MID)

AF:

0.0636

AC:

116

AN:

1824

European-Non Finnish (NFE)

AF:

0.0166

AC:

4141

AN:

249746

Other (OTH)

AF:

0.0492

AC:

1193

AN:

24262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

629

1258

1887

2516

3145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.103

AC:

15732

AN:

152012

Hom.:

1936

Cov.:

AF XY:

0.103

AC XY:

7625

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.297

AC:

12296

AN:

41426

American (AMR)

AF:

0.0701

AC:

1071

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0444

AC:

154

AN:

3470

East Asian (EAS)

AF:

0.0899

AC:

465

AN:

5172

South Asian (SAS)

AF:

0.0499

AC:

240

AN:

4810

European-Finnish (FIN)

AF:

0.0135

AC:

143

AN:

10580

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0158

AC:

1076

AN:

67976

Other (OTH)

AF:

0.0813

AC:

171

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

599

1198

1796

2395

2994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0171

Hom.:

Bravo

AF:

0.118

Asia WGS

AF:

0.0730

AC:

252

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

Jul 15, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.2

(source)

DANN

Benign

0.54

PhyloP100

0.027

PromoterAI

-0.0054

Neutral

(source)

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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chr3-11016994-G-C

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