Variant 3-11016978-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2447 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A1	NM_003042.4 linkuse as main transcript	c.-153-81C>T		intron_variant		ENST00000287766.10
SLC6A1-AS1	NR_046647.1 linkuse as main transcript	n.105+2142G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A1	ENST00000287766.10 linkuse as main transcript	c.-153-81C>T		intron_variant		1	NM_003042.4	P1
SLC6A1-AS1	ENST00000414969.2 linkuse as main transcript	n.105+2142G>A		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 AFR exome

AF:

0.0504

Gnomad4 AMR exome

AF:

0.00379

Gnomad4 ASJ exome

AF:

0.00450

Gnomad4 EAS exome

AF:

0.0102

Gnomad4 SAS exome

AF:

0.0225

Gnomad4 FIN exome

AF:

0.0000812

Gnomad4 NFE exome

AF:

0.000309

Gnomad4 OTH exome

AF:

0.00685

GnomAD4 genome

AF:

0.0161

AC:

2447

AN:

152182

Hom.:

Cov.:

AF XY:

0.0163

AC XY:

1213

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0503

Gnomad4 AMR

AF:

0.00687

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00946

Gnomad4 SAS

AF:

0.0256

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000471

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.00969

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

8.1

DANN

Benign

0.57

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over