rs148429200

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_003042.4(SLC6A1):c.411C>T(p.Asn137Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000916 in 1,613,836 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00088 ( 9 hom. )

Consequence

SLC6A1
NM_003042.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.150

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 3-11018638-C-T is Benign according to our data. Variant chr3-11018638-C-T is described in ClinVar as Benign. ClinVar VariationId is 475480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.15 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00125 (190/152330) while in subpopulation EAS AF = 0.0129 (67/5184). AF 95% confidence interval is 0.0104. There are 2 homozygotes in GnomAd4. There are 110 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 190 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A1	NM_003042.4 link	c.411C>T	p.Asn137Asn	synonymous_variant	Exon 5 of 16	ENST00000287766.10	NP_003033.3	A0A024R2K8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A1	ENST00000287766.10 link	c.411C>T	p.Asn137Asn	synonymous_variant	Exon 5 of 16	1	NM_003042.4	ENSP00000287766.4		P30531

Frequencies

GnomAD3 genomes

AF:

0.00124

AC:

188

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00615

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0133

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00250

AC:

629

AN:

251416

AF XY:

0.00219

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.0101

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0138

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.000881

AC:

1288

AN:

1461506

Hom.:

Cov.:

AF XY:

0.000827

AC XY:

601

AN XY:

727096

show subpopulations

African (AFR)

AF:

0.000239

AC:

AN:

33472

American (AMR)

AF:

0.00944

AC:

422

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0202

AC:

800

AN:

39694

South Asian (SAS)

AF:

0.000116

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000162

AC:

AN:

1111664

Other (OTH)

AF:

0.000497

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

134

200

267

334

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00125

AC:

190

AN:

152330

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

110

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41576

American (AMR)

AF:

0.00640

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0129

AC:

AN:

5184

South Asian (SAS)

AF:

0.00104

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68022

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000327

Hom.:

Bravo

AF:

0.00172

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Nov 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SLC6A1: BP4, BP7, BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 03, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Epilepsy with myoclonic atonic seizures

Benign:1

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

SLC6A1-related disorder

Benign:1

Sep 18, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Inborn genetic diseases

Benign:1

Nov 16, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

7.8

(source)

DANN

Benign

0.91

PhyloP100

0.15

Mutation Taster

=291/9

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over