dbSNP rs187269: GABRB2:c.1077+1265T>C (chr5-161329618-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001371727.1(GABRB2):c.1077+1265T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,068 control chromosomes in the GnomAD database, including 8,865 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.34 ( 8865 hom., cov: 33)

Failed GnomAD Quality Control

Consequence

GABRB2
NM_001371727.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.147

Publications

20 publications found

Variant links:

Genes affected

GABRB2 (HGNC:4082): (gamma-aminobutyric acid type A receptor subunit beta2) The gamma-aminobutyric acid (GABA) A receptor is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. This gene encodes GABA A receptor, beta 2 subunit. It is mapped to chromosome 5q34 in a cluster comprised of genes encoding alpha 1 and gamma 2 subunits of the GABA A receptor. Alternative splicing of this gene generates 2 transcript variants, differing by a 114 bp insertion. [provided by RefSeq, Jul 2008]

GABRB2 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
developmental and epileptic encephalopathy 92
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, Labcorp Genetics (formerly Invitae), G2P
undetermined early-onset epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

GABRB2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371727.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GABRB2	NM_001371727.1	MANE Select	c.1077+1265T>C	intron	N/A	NP_001358656.1	P47870-2
GABRB2	NM_021911.3		c.1077+1265T>C	intron	N/A	NP_068711.1	P47870-2
GABRB2	NM_000813.3		c.1077+1265T>C	intron	N/A	NP_000804.1	P47870-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GABRB2	ENST00000393959.6	TSL:1 MANE Select	c.1077+1265T>C	intron	N/A	ENSP00000377531.1	P47870-2
GABRB2	ENST00000353437.10	TSL:1	c.1077+1265T>C	intron	N/A	ENSP00000274546.6	P47870-1
GABRB2	ENST00000520240.5	TSL:1	c.1077+1265T>C	intron	N/A	ENSP00000429320.1	P47870-1

Frequencies

GnomAD3 genomes

AF:

0.339

AC:

51445

AN:

151950

Hom.:

8849

Cov.:

show subpopulations

Gnomad AFR

AF:

0.378

Gnomad AMI

AF:

0.408

Gnomad AMR

AF:

0.308

Gnomad ASJ

AF:

0.327

Gnomad EAS

AF:

0.205

Gnomad SAS

AF:

0.272

Gnomad FIN

AF:

0.400

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.327

Gnomad OTH

AF:

0.325

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.339

AC:

51482

AN:

152068

Hom.:

8865

Cov.:

AF XY:

0.338

AC XY:

25150

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.378

AC:

15701

AN:

41486

American (AMR)

AF:

0.308

AC:

4712

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.327

AC:

1137

AN:

3472

East Asian (EAS)

AF:

0.205

AC:

1062

AN:

5180

South Asian (SAS)

AF:

0.272

AC:

1312

AN:

4818

European-Finnish (FIN)

AF:

0.400

AC:

4220

AN:

10550

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.327

AC:

22189

AN:

67956

Other (OTH)

AF:

0.321

AC:

679

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1765

3530

5294

7059

8824

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

510

1020

1530

2040

2550

<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:

0.330

Hom.:

3085

Bravo

AF:

0.335

Asia WGS

AF:

0.235

AC:

819

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.8

(source)

DANN

Benign

0.46

PhyloP100

0.15

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over