rs20318

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_021912.5(GABRB3):c.75C>T(p.Pro25Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,562,694 control chromosomes in the GnomAD database, including 27,178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2542 hom., cov: 32)

Exomes 𝑓: 0.18 ( 24636 hom. )

Consequence

GABRB3
NM_021912.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.458

Publications

16 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 15-26773650-G-A is Benign according to our data. Variant chr15-26773650-G-A is described in ClinVar as Benign. ClinVar VariationId is 377904.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.458 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021912.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB3	NM_021912.5		c.75C>T	p.Pro25Pro	synonymous	Exon 1 of 9	NP_068712.1	X5DQY4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GABRB3	ENST00000299267.9	TSL:1	c.75C>T	p.Pro25Pro	synonymous	Exon 1 of 9	ENSP00000299267.4	P28472-2
GABRB3	ENST00000541819.6	TSL:1	c.249-878C>T		intron	N/A	ENSP00000442408.2	F5H7N0
GABRB3	ENST00000638099.1	TSL:5	c.-20+293C>T		intron	N/A	ENSP00000490678.1	A0A1B0GVW3

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23744

AN:

151920

Hom.:

2533

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0391

Gnomad AMI

AF:

0.167

Gnomad AMR

AF:

0.312

Gnomad ASJ

AF:

0.131

Gnomad EAS

AF:

0.315

Gnomad SAS

AF:

0.238

Gnomad FIN

AF:

0.202

Gnomad MID

AF:

0.166

Gnomad NFE

AF:

0.169

Gnomad OTH

AF:

0.165

GnomAD2 exomes

AF:

0.220

AC:

36319

AN:

165162

AF XY:

0.215

show subpopulations

Gnomad AFR exome

AF:

0.0344

Gnomad AMR exome

AF:

0.399

Gnomad ASJ exome

AF:

0.131

Gnomad EAS exome

AF:

0.318

Gnomad FIN exome

AF:

0.199

Gnomad NFE exome

AF:

0.168

Gnomad OTH exome

AF:

0.206

GnomAD4 exome

AF:

0.177

AC:

250332

AN:

1410666

Hom.:

24636

Cov.:

AF XY:

0.179

AC XY:

124876

AN XY:

697086

show subpopulations

African (AFR)

AF:

0.0298

AC:

962

AN:

32336

American (AMR)

AF:

0.388

AC:

14476

AN:

37336

Ashkenazi Jewish (ASJ)

AF:

0.128

AC:

3228

AN:

25246

East Asian (EAS)

AF:

0.337

AC:

12480

AN:

37008

South Asian (SAS)

AF:

0.222

AC:

17806

AN:

80112

European-Finnish (FIN)

AF:

0.198

AC:

9629

AN:

48536

Middle Eastern (MID)

AF:

0.132

AC:

671

AN:

5070

European-Non Finnish (NFE)

AF:

0.167

AC:

181037

AN:

1086558

Other (OTH)

AF:

0.172

AC:

10043

AN:

58464

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

9083

18166

27248

36331

45414

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6530

13060

19590

26120

32650

<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:

0.156

AC:

23756

AN:

152028

Hom.:

2542

Cov.:

AF XY:

0.164

AC XY:

12174

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.0390

AC:

1619

AN:

41564

American (AMR)

AF:

0.313

AC:

4783

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.131

AC:

453

AN:

3466

East Asian (EAS)

AF:

0.314

AC:

1597

AN:

5078

South Asian (SAS)

AF:

0.239

AC:

1153

AN:

4824

European-Finnish (FIN)

AF:

0.202

AC:

2138

AN:

10582

Middle Eastern (MID)

AF:

0.161

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.169

AC:

11468

AN:

67914

Other (OTH)

AF:

0.164

AC:

346

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

959

1917

2876

3834

4793

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

252

504

756

1008

1260

<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:

0.157

Hom.:

709

Bravo

AF:

0.160

Asia WGS

AF:

0.255

AC:

861

AN:

3376

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

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

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

0.46

PromoterAI

-0.0048

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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