15-26560917-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_000814.6(GABRB3):c.1080+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,612,842 control chromosomes in the GnomAD database, including 82,503 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10564 hom., cov: 33)

Exomes 𝑓: 0.30 ( 71939 hom. )

Consequence

GABRB3
NM_000814.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.0120

Publications

13 publications found

Variant links:

Genes affected

GABRB3 (HGNC:4083): (gamma-aminobutyric acid type A receptor subunit beta3) This gene encodes a member of the ligand-gated ionic channel family. The encoded protein is one the subunits of a multi-subunit chloride channel that serves as the receptor for gamma-aminobutyric acid, a major inhibitory neurotransmitter of the mammalian nervous system. This gene is located on the long arm of chromosome 15 in a cluster with two other genes encoding related subunits of the family. This gene may be associated with the pathogenesis of several disorders including Angelman syndrome, Prader-Willi syndrome, nonsyndromic orofacial clefts, epilepsy and autism. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2013]

GABRB3 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 43
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
epilepsy, childhood absence, susceptibility to, 5
Inheritance: AD, Unknown Classification: DEFINITIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
childhood absence epilepsy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Lennox-Gastaut syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

GABRB3 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=-0.92).

BP6

Variant 15-26560917-T-C is Benign according to our data. Variant chr15-26560917-T-C is described in ClinVar as Benign. ClinVar VariationId is 256818.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000814.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GABRB3	NM_000814.6	MANE Select	c.1080+15A>G	intron	N/A	NP_000805.1	P28472-1
GABRB3	NM_021912.5		c.1080+15A>G	intron	N/A	NP_068712.1	X5DQY4
GABRB3	NM_001191321.3		c.867+15A>G	intron	N/A	NP_001178250.1	P28472-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GABRB3	ENST00000311550.10	TSL:1 MANE Select	c.1080+15A>G	intron	N/A	ENSP00000308725.5	P28472-1
GABRB3	ENST00000541819.6	TSL:1	c.1248+15A>G	intron	N/A	ENSP00000442408.2	F5H7N0
GABRB3	ENST00000299267.9	TSL:1	c.1080+15A>G	intron	N/A	ENSP00000299267.4	P28472-2

Frequencies

GnomAD3 genomes

AF:

0.352

AC:

53536

AN:

151876

Hom.:

10550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.487

Gnomad AMI

AF:

0.309

Gnomad AMR

AF:

0.308

Gnomad ASJ

AF:

0.278

Gnomad EAS

AF:

0.755

Gnomad SAS

AF:

0.395

Gnomad FIN

AF:

0.276

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.265

Gnomad OTH

AF:

0.324

GnomAD2 exomes

AF:

0.344

AC:

86488

AN:

251448

AF XY:

0.337

show subpopulations

Gnomad AFR exome

AF:

0.488

Gnomad AMR exome

AF:

0.355

Gnomad ASJ exome

AF:

0.278

Gnomad EAS exome

AF:

0.756

Gnomad FIN exome

AF:

0.287

Gnomad NFE exome

AF:

0.261

Gnomad OTH exome

AF:

0.314

GnomAD4 exome

AF:

0.298

AC:

435670

AN:

1460848

Hom.:

71939

Cov.:

AF XY:

0.299

AC XY:

217214

AN XY:

726734

show subpopulations

African (AFR)

AF:

0.490

AC:

16375

AN:

33452

American (AMR)

AF:

0.349

AC:

15586

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.274

AC:

7163

AN:

26134

East Asian (EAS)

AF:

0.775

AC:

30758

AN:

39700

South Asian (SAS)

AF:

0.380

AC:

32782

AN:

86202

European-Finnish (FIN)

AF:

0.281

AC:

15027

AN:

53414

Middle Eastern (MID)

AF:

0.269

AC:

1375

AN:

5116

European-Non Finnish (NFE)

AF:

0.267

AC:

297047

AN:

1111834

Other (OTH)

AF:

0.324

AC:

19557

AN:

60280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

17720

35439

53159

70878

88598

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10390

20780

31170

41560

51950

<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:

0.353

AC:

53602

AN:

151994

Hom.:

10564

Cov.:

AF XY:

0.355

AC XY:

26348

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.487

AC:

20178

AN:

41468

American (AMR)

AF:

0.309

AC:

4717

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.278

AC:

963

AN:

3470

East Asian (EAS)

AF:

0.755

AC:

3883

AN:

5144

South Asian (SAS)

AF:

0.396

AC:

1907

AN:

4820

European-Finnish (FIN)

AF:

0.276

AC:

2919

AN:

10572

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.265

AC:

17995

AN:

67934

Other (OTH)

AF:

0.323

AC:

682

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1715

3431

5146

6862

8577

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

512

1024

1536

2048

2560

<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:

0.296

Hom.:

27895

Bravo

AF:

0.363

Asia WGS

AF:

0.529

AC:

1839

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

Developmental and epileptic encephalopathy, 43 (1)

Epilepsy, childhood absence, susceptibility to, 1;C2677087:Epilepsy, childhood absence, susceptibility to, 5 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.25

(source)

DANN

Benign

0.33

PhyloP100

0.012

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over