5-161338199-C-T

Variant names:

• chr5-161338199-C-T
• rs2617503
• NM_001371727.1:c.542-1430G>A

Variant summary

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

The NM_001371727.1(GABRB2):​c.542-1430G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 151,968 control chromosomes in the GnomAD database, including 23,144 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 0.52 (23144 hom., cov: 32)
• Consequence: GABRB2 NM_001371727.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320
• Publications: 4 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 (AFR) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB2	NM_001371727.1	c.542-1430G>A		intron_variant	Intron 5 of 9	ENST00000393959.6	NP_001358656.1
GABRB2	NM_021911.3	c.542-1430G>A		intron_variant	Intron 6 of 10		NP_068711.1
GABRB2	NM_000813.3	c.542-1430G>A		intron_variant	Intron 6 of 9		NP_000804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB2	ENST00000393959.6	c.542-1430G>A		intron_variant	Intron 5 of 9	1	NM_001371727.1	ENSP00000377531.1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79382 AN: 151850 Hom.: 23098 Cov.: 32

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.517

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

GnomAD4 genome AF: 0.523 AC: 79486 AN: 151968 Hom.: 23144 Cov.: 32 AF XY: 0.525 AC XY: 38966 AN XY: 74278

African (AFR) AF: 0.792 AC: 32872 AN: 41490

American (AMR) AF: 0.568 AC: 8672 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1213 AN: 3468

East Asian (EAS) AF: 0.453 AC: 2339 AN: 5158

South Asian (SAS) AF: 0.401 AC: 1930 AN: 4816

European-Finnish (FIN) AF: 0.472 AC: 4982 AN: 10548

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25904 AN: 67906

Other (OTH) AF: 0.516 AC: 1089 AN: 2110

Alfa AF: 0.421 Hom.: 16059

Bravo AF: 0.547

Asia WGS AF: 0.445 AC: 1547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.15
PhyloP100		0.032
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: rs2617503; hg19: chr5-160765206;