4-47355666-G-A

Variant names:

• chr4-47355666-G-A
• rs728293
• NM_000812.4:c.544+35457G>A

Variant summary

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

The NM_000812.4(GABRB1):​c.544+35457G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 151,960 control chromosomes in the GnomAD database, including 13,376 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 0.41 (13376 hom., cov: 32)
• Consequence: GABRB1 NM_000812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.337
• Publications: 4 publications found

Genes affected

GABRB1 (HGNC:4081): (gamma-aminobutyric acid type A receptor subunit beta1) 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 1 subunit. It is mapped to chromosome 4p12 in a cluster comprised of genes encoding alpha 4, alpha 2 and gamma 1 subunits of the GABA A receptor. Alteration of this gene is implicated in the pathogenetics of schizophrenia. [provided by RefSeq, Jul 2008]

GABRB1 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 45

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000812.4. 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
	GABRB1	NM_000812.4	MANE Select	c.544+35457G>A		intron	N/A	NP_000803.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB1	ENST00000295454.8	TSL:1 MANE Select	c.544+35457G>A		intron	N/A	ENSP00000295454.3
	GABRB1	ENST00000510909.1	TSL:4	n.*212+35457G>A		intron	N/A	ENSP00000426766.1

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62395 AN: 151840 Hom.: 13364 Cov.: 32

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.0225

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.411 AC: 62436 AN: 151960 Hom.: 13376 Cov.: 32 AF XY: 0.400 AC XY: 29706 AN XY: 74284

African (AFR) AF: 0.428 AC: 17717 AN: 41434

American (AMR) AF: 0.384 AC: 5854 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1560 AN: 3466

East Asian (EAS) AF: 0.0226 AC: 117 AN: 5180

South Asian (SAS) AF: 0.312 AC: 1502 AN: 4816

European-Finnish (FIN) AF: 0.296 AC: 3124 AN: 10564

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31297 AN: 67938

Other (OTH) AF: 0.427 AC: 900 AN: 2110

Alfa AF: 0.442 Hom.: 6027

Bravo AF: 0.420

Asia WGS AF: 0.195 AC: 682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	14
DANN	Benign	0.56
PhyloP100		0.34
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: rs728293; hg19: chr4-47357683;