rs1816072

Variant names:

• chr5-161332649-A-G
• rs1816072
• NM_001371727.1:c.833-1522T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001371727.1(GABRB2):​c.833-1522T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,954 control chromosomes in the GnomAD database, including 16,530 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 0.45 (16530 hom., cov: 31)
• Consequence: GABRB2 NM_001371727.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.424
• Publications: 25 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.646 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB2	NM_001371727.1	MANE Select	c.833-1522T>C		intron	N/A	NP_001358656.1	P47870-2
	GABRB2	NM_021911.3		c.833-1522T>C		intron	N/A	NP_068711.1	P47870-2
	GABRB2	NM_000813.3		c.833-1522T>C		intron	N/A	NP_000804.1	P47870-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB2	ENST00000393959.6	TSL:1 MANE Select	c.833-1522T>C		intron	N/A	ENSP00000377531.1	P47870-2
	GABRB2	ENST00000353437.10	TSL:1	c.833-1522T>C		intron	N/A	ENSP00000274546.6	P47870-1
	GABRB2	ENST00000520240.5	TSL:1	c.833-1522T>C		intron	N/A	ENSP00000429320.1	P47870-1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68007 AN: 151834 Hom.: 16502 Cov.: 31

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.435

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.448 AC: 68080 AN: 151954 Hom.: 16530 Cov.: 31 AF XY: 0.446 AC XY: 33143 AN XY: 74278

African (AFR) AF: 0.652 AC: 27019 AN: 41426

American (AMR) AF: 0.383 AC: 5845 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1191 AN: 3460

East Asian (EAS) AF: 0.398 AC: 2055 AN: 5158

South Asian (SAS) AF: 0.327 AC: 1573 AN: 4812

European-Finnish (FIN) AF: 0.419 AC: 4415 AN: 10548

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24581 AN: 67968

Other (OTH) AF: 0.432 AC: 912 AN: 2112

Alfa AF: 0.388 Hom.: 15258

Bravo AF: 0.459

Asia WGS AF: 0.370 AC: 1289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.7
DANN	Benign	0.38
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1816072; hg19: chr5-160759656;