5-161331961-C-G

Variant names:

• chr5-161331961-C-G
• rs13178374
• NM_001371727.1:c.833-834G>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.833-834G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0246 in 151,718 control chromosomes in the GnomAD database, including 66 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 0.025 (66 hom., cov: 31)
• Consequence: GABRB2 NM_001371727.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.930
• Publications: 3 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB2	NM_001371727.1	c.833-834G>C		intron_variant	Intron 7 of 9	ENST00000393959.6	NP_001358656.1
GABRB2	NM_021911.3	c.833-834G>C		intron_variant	Intron 8 of 10		NP_068711.1
GABRB2	NM_000813.3	c.833-834G>C		intron_variant	Intron 8 of 9		NP_000804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB2	ENST00000393959.6	c.833-834G>C		intron_variant	Intron 7 of 9	1	NM_001371727.1	ENSP00000377531.1

Frequencies

GnomAD3 genomes AF: 0.0247 AC: 3737 AN: 151598 Hom.: 66 Cov.: 31

Gnomad AFR AF: 0.00683

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.0331

Gnomad ASJ AF: 0.0109

Gnomad EAS AF: 0.0749

Gnomad SAS AF: 0.0119

Gnomad FIN AF: 0.0181

Gnomad MID AF: 0.00962

Gnomad NFE AF: 0.0323

Gnomad OTH AF: 0.0371

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

GnomAD4 genome AF: 0.0246 AC: 3739 AN: 151718 Hom.: 66 Cov.: 31 AF XY: 0.0236 AC XY: 1751 AN XY: 74118

African (AFR) AF: 0.00681 AC: 282 AN: 41396

American (AMR) AF: 0.0331 AC: 505 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.0109 AC: 38 AN: 3472

East Asian (EAS) AF: 0.0750 AC: 383 AN: 5104

South Asian (SAS) AF: 0.0121 AC: 58 AN: 4786

European-Finnish (FIN) AF: 0.0181 AC: 191 AN: 10540

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.0323 AC: 2196 AN: 67884

Other (OTH) AF: 0.0362 AC: 76 AN: 2100

Alfa AF: 0.00973 Hom.: 2

Bravo AF: 0.0273

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.6
DANN	Benign	0.34
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism

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: rs13178374; hg19: chr5-160758968;