NM_001371727.1:c.832+1803A>G

Variant names:

• chr5-161332949-T-C
• rs1816071
• NM_001371727.1:c.832+1803A>G

Variant summary

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

The NM_001371727.1(GABRB2):​c.832+1803A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 151,930 control chromosomes in the GnomAD database, including 10,237 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 0.37 (10237 hom., cov: 31)
• Consequence: GABRB2 NM_001371727.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 26 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):

• developmental and epileptic encephalopathy 92

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Illumina, 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB2	NM_001371727.1	MANE Select	c.832+1803A>G		intron	N/A	NP_001358656.1
	GABRB2	NM_021911.3		c.832+1803A>G		intron	N/A	NP_068711.1
	GABRB2	NM_000813.3		c.832+1803A>G		intron	N/A	NP_000804.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB2	ENST00000393959.6	TSL:1 MANE Select	c.832+1803A>G		intron	N/A	ENSP00000377531.1
	GABRB2	ENST00000353437.10	TSL:1	c.832+1803A>G		intron	N/A	ENSP00000274546.6
	GABRB2	ENST00000520240.5	TSL:1	c.832+1803A>G		intron	N/A	ENSP00000429320.1

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55453 AN: 151812 Hom.: 10221 Cov.: 31

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.349

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.365 AC: 55492 AN: 151930 Hom.: 10237 Cov.: 31 AF XY: 0.364 AC XY: 27061 AN XY: 74246

African (AFR) AF: 0.385 AC: 15944 AN: 41408

American (AMR) AF: 0.342 AC: 5220 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1175 AN: 3470

East Asian (EAS) AF: 0.281 AC: 1451 AN: 5166

South Asian (SAS) AF: 0.284 AC: 1364 AN: 4810

European-Finnish (FIN) AF: 0.435 AC: 4593 AN: 10550

Middle Eastern (MID) AF: 0.341 AC: 99 AN: 290

European-Non Finnish (NFE) AF: 0.361 AC: 24513 AN: 67948

Other (OTH) AF: 0.358 AC: 755 AN: 2106

Alfa AF: 0.361 Hom.: 27198

Bravo AF: 0.364

Asia WGS AF: 0.273 AC: 950 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.21
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs1816071; hg19: chr5-160759956;