chr5-161333168-C-A

Variant names:

• chr5-161333168-C-A
• rs6556547
• NM_001371727.1:c.832+1584G>T

Variant summary

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

The NM_021911.3(GABRB2):​c.832+1584G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0924 in 151,938 control chromosomes in the GnomAD database, including 734 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 0.092 (734 hom., cov: 32)
• Consequence: GABRB2 NM_021911.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70
• Publications: 14 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021911.3. 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.832+1584G>T		intron	N/A	NP_001358656.1
	GABRB2	NM_021911.3		c.832+1584G>T		intron	N/A	NP_068711.1
	GABRB2	NM_000813.3		c.832+1584G>T		intron	N/A	NP_000804.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB2	ENST00000393959.6	TSL:1 MANE Select	c.832+1584G>T		intron	N/A	ENSP00000377531.1
	GABRB2	ENST00000353437.10	TSL:1	c.832+1584G>T		intron	N/A	ENSP00000274546.6
	GABRB2	ENST00000520240.5	TSL:1	c.832+1584G>T		intron	N/A	ENSP00000429320.1

Frequencies

GnomAD3 genomes AF: 0.0924 AC: 14032 AN: 151818 Hom.: 732 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.0198

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0744

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.0428

Gnomad MID AF: 0.0641

Gnomad NFE AF: 0.0690

Gnomad OTH AF: 0.0748

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

GnomAD4 genome AF: 0.0924 AC: 14044 AN: 151938 Hom.: 734 Cov.: 32 AF XY: 0.0935 AC XY: 6942 AN XY: 74250

African (AFR) AF: 0.121 AC: 5015 AN: 41460

American (AMR) AF: 0.123 AC: 1883 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.0744 AC: 258 AN: 3470

East Asian (EAS) AF: 0.163 AC: 844 AN: 5168

South Asian (SAS) AF: 0.148 AC: 711 AN: 4792

European-Finnish (FIN) AF: 0.0428 AC: 452 AN: 10552

Middle Eastern (MID) AF: 0.0616 AC: 18 AN: 292

European-Non Finnish (NFE) AF: 0.0690 AC: 4688 AN: 67936

Other (OTH) AF: 0.0745 AC: 157 AN: 2108

Alfa AF: 0.0390 Hom.: 50

Bravo AF: 0.0978

Asia WGS AF: 0.134 AC: 468 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.9
DANN	Benign	0.24
PhyloP100		1.7
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: rs6556547; hg19: chr5-160760175;