NM_001371727.1:c.680-263G>A

Variant names:

• chr5-161335167-C-T
• rs967771
• NM_001371727.1:c.680-263G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001371727.1(GABRB2):​c.680-263G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,022 control chromosomes in the GnomAD database, including 2,554 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2554 hom., cov: 32)
• Consequence: GABRB2 NM_001371727.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.05
• Publications: 7 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):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy 92

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, Labcorp Genetics (formerly Invitae), G2P
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 5-161335167-C-T is Benign according to our data. Variant chr5-161335167-C-T is described in ClinVar as Benign. ClinVar VariationId is 668791.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371727.1. 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.680-263G>A		intron	N/A	NP_001358656.1	P47870-2
	GABRB2	NM_021911.3		c.680-263G>A		intron	N/A	NP_068711.1	P47870-2
	GABRB2	NM_000813.3		c.680-263G>A		intron	N/A	NP_000804.1	P47870-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB2	ENST00000393959.6	TSL:1 MANE Select	c.680-263G>A		intron	N/A	ENSP00000377531.1	P47870-2
	GABRB2	ENST00000353437.10	TSL:1	c.680-263G>A		intron	N/A	ENSP00000274546.6	P47870-1
	GABRB2	ENST00000520240.5	TSL:1	c.680-263G>A		intron	N/A	ENSP00000429320.1	P47870-1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24542 AN: 151904 Hom.: 2549 Cov.: 32

Gnomad AFR AF: 0.0435

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.0914

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.161 AC: 24549 AN: 152022 Hom.: 2554 Cov.: 32 AF XY: 0.158 AC XY: 11719 AN XY: 74298

African (AFR) AF: 0.0434 AC: 1800 AN: 41510

American (AMR) AF: 0.145 AC: 2221 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 894 AN: 3468

East Asian (EAS) AF: 0.132 AC: 677 AN: 5148

South Asian (SAS) AF: 0.0929 AC: 447 AN: 4810

European-Finnish (FIN) AF: 0.198 AC: 2088 AN: 10548

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15931 AN: 67938

Other (OTH) AF: 0.139 AC: 293 AN: 2106

Alfa AF: 0.201 Hom.: 4796

Bravo AF: 0.153

Asia WGS AF: 0.100 AC: 347 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.24
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs967771; hg19: chr5-160762174; COSMIC: COSV50905360;