5-161850893-A-T

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.74+9A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0616 in 1,610,000 control chromosomes in the GnomAD database, including 3,551 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 302 hom., cov: 32)

Exomes 𝑓: 0.062 ( 3249 hom. )

Consequence

GABRA1
NM_001127644.2 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.34

Publications

5 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
epilepsy
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=-0.68).

BP6

Variant 5-161850893-A-T is Benign according to our data. Variant chr5-161850893-A-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 129124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127644.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GABRA1	NM_001127644.2	MANE Select	c.74+9A>T	intron	N/A	NP_001121116.1	P14867
GABRA1	NM_000806.5		c.74+9A>T	intron	N/A	NP_000797.2	A8K177
GABRA1	NM_001127643.2		c.74+9A>T	intron	N/A	NP_001121115.1	P14867

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GABRA1	ENST00000393943.10	TSL:1 MANE Select	c.74+9A>T	intron	N/A	ENSP00000377517.4	P14867
GABRA1	ENST00000023897.10	TSL:1	c.74+9A>T	intron	N/A	ENSP00000023897.6	P14867
GABRA1	ENST00000428797.7	TSL:1	c.74+9A>T	intron	N/A	ENSP00000393097.2	P14867

Frequencies

GnomAD3 genomes

AF:

0.0552

AC:

8399

AN:

152092

Hom.:

298

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0268

Gnomad AMI

AF:

0.0658

Gnomad AMR

AF:

0.0779

Gnomad ASJ

AF:

0.100

Gnomad EAS

AF:

0.0880

Gnomad SAS

AF:

0.121

Gnomad FIN

AF:

0.0442

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0590

Gnomad OTH

AF:

0.0681

GnomAD2 exomes

AF:

0.0741

AC:

18605

AN:

251036

AF XY:

0.0756

show subpopulations

Gnomad AFR exome

AF:

0.0269

Gnomad AMR exome

AF:

0.0999

Gnomad ASJ exome

AF:

0.102

Gnomad EAS exome

AF:

0.0853

Gnomad FIN exome

AF:

0.0510

Gnomad NFE exome

AF:

0.0637

Gnomad OTH exome

AF:

0.0778

GnomAD4 exome

AF:

0.0623

AC:

90796

AN:

1457788

Hom.:

3249

Cov.:

AF XY:

0.0638

AC XY:

46294

AN XY:

725526

show subpopulations

African (AFR)

AF:

0.0286

AC:

956

AN:

33384

American (AMR)

AF:

0.0980

AC:

4379

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.100

AC:

2614

AN:

26114

East Asian (EAS)

AF:

0.107

AC:

4248

AN:

39680

South Asian (SAS)

AF:

0.108

AC:

9291

AN:

86152

European-Finnish (FIN)

AF:

0.0515

AC:

2748

AN:

53408

Middle Eastern (MID)

AF:

0.128

AC:

738

AN:

5754

European-Non Finnish (NFE)

AF:

0.0557

AC:

61784

AN:

1108400

Other (OTH)

AF:

0.0671

AC:

4038

AN:

60192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

3942

7884

11825

15767

19709

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2374

4748

7122

9496

11870

<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:

0.0553

AC:

8414

AN:

152212

Hom.:

302

Cov.:

AF XY:

0.0567

AC XY:

4220

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0267

AC:

1111

AN:

41548

American (AMR)

AF:

0.0778

AC:

1189

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.100

AC:

348

AN:

3470

East Asian (EAS)

AF:

0.0882

AC:

456

AN:

5170

South Asian (SAS)

AF:

0.121

AC:

584

AN:

4818

European-Finnish (FIN)

AF:

0.0442

AC:

469

AN:

10618

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0590

AC:

4011

AN:

67994

Other (OTH)

AF:

0.0735

AC:

155

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

406

811

1217

1622

2028

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

208

312

416

520

<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:

0.0486

Hom.:

Bravo

AF:

0.0589

Asia WGS

AF:

0.139

AC:

483

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Epilepsy, idiopathic generalized, susceptibility to, 13 (1)

Idiopathic generalized epilepsy;C1970160:Epilepsy, childhood absence 4;C4013473:Epilepsy, idiopathic generalized, susceptibility to, 13 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

1.3

PromoterAI

0.0060

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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