chr5-161895648-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001127644.2(GABRA1):c.857-18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0637 in 1,595,954 control chromosomes in the GnomAD database, including 3,487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 351 hom., cov: 31)

Exomes 𝑓: 0.064 ( 3136 hom. )

Consequence

GABRA1
NM_001127644.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.28

Publications

4 publications found

Variant links:

Genes affected

GABRA1 (HGNC:4075): (gamma-aminobutyric acid type A receptor subunit alpha1) This gene encodes a gamma-aminobutyric acid (GABA) receptor. GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. Mutations in this gene cause juvenile myoclonic epilepsy and childhood absence epilepsy type 4. Multiple transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]

GABRA1 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 19
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
epilepsy, idiopathic generalized, susceptibility to, 13
Inheritance: AD Classification: STRONG Submitted by: G2P
Dravet syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
juvenile myoclonic epilepsy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

GABRA1 links:

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=-0.83).

BP6

Variant 5-161895648-T-C is Benign according to our data. Variant chr5-161895648-T-C is described in ClinVar as [Benign]. Clinvar id is 256816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRA1	NM_001127644.2 link	c.857-18T>C		intron_variant	Intron 8 of 9	ENST00000393943.10	NP_001121116.1	P14867

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRA1	ENST00000393943.10 link	c.857-18T>C		intron_variant	Intron 8 of 9	1	NM_001127644.2	ENSP00000377517.4		P14867

Frequencies

GnomAD3 genomes

AF:

0.0631

AC:

9438

AN:

149568

Hom.:

344

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0519

Gnomad AMI

AF:

0.0658

Gnomad AMR

AF:

0.0824

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.0858

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.0447

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0599

Gnomad OTH

AF:

0.0733

GnomAD2 exomes

AF:

0.0922

AC:

18562

AN:

201228

AF XY:

0.0936

show subpopulations

Gnomad AFR exome

AF:

0.0635

Gnomad AMR exome

AF:

0.119

Gnomad ASJ exome

AF:

0.125

Gnomad EAS exome

AF:

0.0948

Gnomad FIN exome

AF:

0.0657

Gnomad NFE exome

AF:

0.0806

Gnomad OTH exome

AF:

0.0934

GnomAD4 exome

AF:

0.0637

AC:

92186

AN:

1446288

Hom.:

3136

Cov.:

AF XY:

0.0651

AC XY:

46812

AN XY:

719592

show subpopulations

African (AFR)

AF:

0.0560

AC:

1855

AN:

33136

American (AMR)

AF:

0.100

AC:

4409

AN:

43996

Ashkenazi Jewish (ASJ)

AF:

0.110

AC:

2856

AN:

25950

East Asian (EAS)

AF:

0.104

AC:

4092

AN:

39440

South Asian (SAS)

AF:

0.105

AC:

8927

AN:

85416

European-Finnish (FIN)

AF:

0.0518

AC:

2732

AN:

52696

Middle Eastern (MID)

AF:

0.131

AC:

751

AN:

5736

European-Non Finnish (NFE)

AF:

0.0567

AC:

62401

AN:

1100080

Other (OTH)

AF:

0.0696

AC:

4163

AN:

59838

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

4071

8143

12214

16286

20357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2422

4844

7266

9688

12110

<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:

0.0632

AC:

9459

AN:

149666

Hom.:

351

Cov.:

AF XY:

0.0643

AC XY:

4705

AN XY:

73142

show subpopulations

African (AFR)

AF:

0.0519

AC:

2078

AN:

40014

American (AMR)

AF:

0.0824

AC:

1246

AN:

15122

Ashkenazi Jewish (ASJ)

AF:

0.107

AC:

370

AN:

3460

East Asian (EAS)

AF:

0.0860

AC:

441

AN:

5128

South Asian (SAS)

AF:

0.118

AC:

565

AN:

4788

European-Finnish (FIN)

AF:

0.0447

AC:

467

AN:

10440

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0599

AC:

4038

AN:

67428

Other (OTH)

AF:

0.0788

AC:

164

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

457

915

1372

1830

2287

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<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:

0.0533

Hom.:

130

Bravo

AF:

0.0673

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Idiopathic generalized epilepsy;C1970160:Epilepsy, childhood absence 4;C4013473:Epilepsy, idiopathic generalized, susceptibility to, 13

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Mar 03, 2015

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

-0.83

CADD

Benign

3.0

(source)

DANN

Benign

0.52

PhyloP100

-1.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over