rs6556547

chr5-161333168-C-Achr5-161333168-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001371727.1(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_001371727.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRB2	NM_001371727.1	c.832+1584G>T		intron_variant		ENST00000393959.6
GABRB2	NM_000813.3	c.832+1584G>T		intron_variant
GABRB2	NM_021911.3	c.832+1584G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRB2	ENST00000393959.6	c.832+1584G>T		intron_variant		1	NM_001371727.1

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

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.0744

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.0428

Gnomad4 NFE AF: 0.0690

Gnomad4 OTH AF: 0.0745

Alfa AF: 0.0358 Hom.: 42

Bravo AF: 0.0978

Asia WGS AF: 0.134 AC: 468 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	4.9
Dann	Benign	0.24

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

LitVar

Other links and lift over

dbSNP: rs6556547; hg19: chr5-160760175;