chr5-161331648-A-G

Variant names:

• chr5-161331648-A-G
• rs194072
• NM_001371727.1:c.833-521T>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.833-521T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,080 control chromosomes in the GnomAD database, including 1,480 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 0.14 (1480 hom., cov: 31)
• Consequence: GABRB2 NM_001371727.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.231
• Publications: 18 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB2	NM_001371727.1	c.833-521T>C		intron_variant	Intron 7 of 9	ENST00000393959.6	NP_001358656.1
GABRB2	NM_021911.3	c.833-521T>C		intron_variant	Intron 8 of 10		NP_068711.1
GABRB2	NM_000813.3	c.833-521T>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.833-521T>C		intron_variant	Intron 7 of 9	1	NM_001371727.1	ENSP00000377531.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20946 AN: 151962 Hom.: 1477 Cov.: 31

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.138 AC: 20961 AN: 152080 Hom.: 1480 Cov.: 31 AF XY: 0.138 AC XY: 10294 AN XY: 74330

African (AFR) AF: 0.131 AC: 5448 AN: 41480

American (AMR) AF: 0.163 AC: 2492 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 442 AN: 3470

East Asian (EAS) AF: 0.166 AC: 857 AN: 5150

South Asian (SAS) AF: 0.160 AC: 767 AN: 4798

European-Finnish (FIN) AF: 0.128 AC: 1353 AN: 10590

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9242 AN: 68008

Other (OTH) AF: 0.111 AC: 235 AN: 2112

Alfa AF: 0.138 Hom.: 6368

Bravo AF: 0.140

Asia WGS AF: 0.148 AC: 515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.5
DANN	Benign	0.55
PhyloP100		0.23
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: rs194072; hg19: chr5-160758655; COSMIC: COSV107283276;