Genetic Variant SLC6A1:c.-215-8225C>T (chr3-11007447-C-T) – 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.-215-8225C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,178 control chromosomes in the GnomAD database, including 11,433 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 0.38 ( 11422 hom., cov: 33)

Exomes 𝑓: 0.51 ( 11 hom. )

Consequence

SLC6A1
NM_003042.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.361

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:

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=-0.96).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 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
SLC6A1	NM_003042.4	MANE Select	c.-215-8225C>T	intron	N/A	NP_003033.3
SLC6A1	NM_001348250.2		c.-154-8225C>T	intron	N/A	NP_001335179.1
SLC6A1	NM_001348251.2		c.-324-8225C>T	intron	N/A	NP_001335180.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SLC6A1	ENST00000287766.10	TSL:1 MANE Select	c.-215-8225C>T	intron	N/A	ENSP00000287766.4
SLC6A1	ENST00000642201.1		c.-25-9740C>T	intron	N/A	ENSP00000494778.1
SLC6A1	ENST00000642515.1		c.-1222-5152C>T	intron	N/A	ENSP00000496348.1

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

58308

AN:

151980

Hom.:

11411

Cov.:

show subpopulations

Gnomad AFR

AF:

0.404

Gnomad AMI

AF:

0.422

Gnomad AMR

AF:

0.296

Gnomad ASJ

AF:

0.381

Gnomad EAS

AF:

0.464

Gnomad SAS

AF:

0.393

Gnomad FIN

AF:

0.365

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.387

Gnomad OTH

AF:

0.387

GnomAD4 exome

AF:

0.512

AC:

AN:

Hom.:

AF XY:

0.441

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.485

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.536

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:

0.384

AC:

58355

AN:

152098

Hom.:

11422

Cov.:

AF XY:

0.383

AC XY:

28443

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.404

AC:

16764

AN:

41486

American (AMR)

AF:

0.296

AC:

4521

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.381

AC:

1320

AN:

3468

East Asian (EAS)

AF:

0.463

AC:

2391

AN:

5160

South Asian (SAS)

AF:

0.392

AC:

1891

AN:

4824

European-Finnish (FIN)

AF:

0.365

AC:

3857

AN:

10560

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.387

AC:

26310

AN:

67994

Other (OTH)

AF:

0.388

AC:

820

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1844

3688

5533

7377

9221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

560

1120

1680

2240

2800

<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:

0.387

Hom.:

23855

Bravo

AF:

0.378

Asia WGS

AF:

0.410

AC:

1425

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.64

(source)

DANN

Benign

0.53

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