3-11016978-C-T

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

2

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

Genome browser will be placed here

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
SLC6A1NM_003042.4 linkc.-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
SLC6A1ENST00000287766.10 linkc.-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.:
48
Cov.:
32
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.:
41
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:
59
AN:
15582
Ashkenazi Jewish (ASJ)
AF:
0.00450
AC:
55
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:
2
AN:
24636
Middle Eastern (MID)
AF:
0.00582
AC:
10
AN:
1718
European-Non Finnish (NFE)
AF:
0.000309
AC:
72
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
0
100
200
301
401
501
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
24
48
72
96
120
<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:
0.0161
AC:
2447
AN:
152182
Hom.:
49
Cov.:
32
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:
16
AN:
3472
East Asian (EAS)
AF:
0.00946
AC:
49
AN:
5178
South Asian (SAS)
AF:
0.0256
AC:
123
AN:
4804
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10616
Middle Eastern (MID)
AF:
0.0102
AC:
3
AN:
294
European-Non Finnish (NFE)
AF:
0.000471
AC:
32
AN:
68012
Other (OTH)
AF:
0.0142
AC:
30
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.496
Heterozygous variant carriers
0
112
224
335
447
559
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
34
68
102
136
170
<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:
0.0106
Hom.:
2
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
DANN
Benign
0.57
PhyloP100
-0.65
PromoterAI
-0.023
Neutral
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs41388950; hg19: chr3-11058664; API