Genetic Variant SLC6A1:c.-153-81C>T (chr3-11016978-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003042.4(SLC6A1):c.-153-81C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00841 in 539,788 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 49 hom., cov: 32)

Exomes 𝑓: 0.0054 ( 41 hom. )

Consequence

SLC6A1
NM_003042.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.649

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:

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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=-0.89).

BP6

Variant 3-11016978-C-T is Benign according to our data. Variant chr3-11016978-C-T is described in ClinVar as [Benign]. Clinvar id is 1226679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0161 (2447/152182) while in subpopulation AFR AF = 0.0503 (2089/41498). AF 95% confidence interval is 0.0485. There are 49 homozygotes in GnomAd4. There are 1213 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2447 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A1	NM_003042.4 link	c.-153-81C>T		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.-153-81C>T		intron_variant	Intron 2 of 15	1	NM_003042.4	ENSP00000287766.4		P30531

Frequencies

GnomAD3 genomes

AF:

0.0161

AC:

2445

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0504

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00688

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00944

Gnomad SAS

AF:

0.0256

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.0144

GnomAD4 exome

AF:

0.00540

AC:

2095

AN:

387606

Hom.:

AF XY:

0.00607

AC XY:

1230

AN XY:

202652

show subpopulations

African (AFR)

AF:

0.0504

AC:

564

AN:

11194

American (AMR)

AF:

0.00379

AC:

AN:

15582

Ashkenazi Jewish (ASJ)

AF:

0.00450

AC:

AN:

12228

East Asian (EAS)

AF:

0.0102

AC:

270

AN:

26418

South Asian (SAS)

AF:

0.0225

AC:

907

AN:

40270

European-Finnish (FIN)

AF:

0.0000812

AC:

AN:

24636

Middle Eastern (MID)

AF:

0.00582

AC:

AN:

1718

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

232798

Other (OTH)

AF:

0.00685

AC:

156

AN:

22762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

100

200

301

401

501

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0161

AC:

2447

AN:

152182

Hom.:

Cov.:

AF XY:

0.0163

AC XY:

1213

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.0503

AC:

2089

AN:

41498

American (AMR)

AF:

0.00687

AC:

105

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00461

AC:

AN:

3472

East Asian (EAS)

AF:

0.00946

AC:

AN:

5178

South Asian (SAS)

AF:

0.0256

AC:

123

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000471

AC:

AN:

68012

Other (OTH)

AF:

0.0142

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

112

224

335

447

559

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0106

Hom.:

Bravo

AF:

0.0180

Asia WGS

AF:

0.0320

AC:

112

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

- -

Jul 26, 2018

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

-0.89

CADD

Benign

8.1

(source)

DANN

Benign

0.57

PhyloP100

-0.65

PromoterAI

-0.023

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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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3-11016978-C-T

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