4-47164764-T-G

Variant names:

• chr4-47164764-T-G
• rs989808
• NM_000812.4:c.461+3295T>G

Variant summary

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

The NM_000812.4(GABRB1):​c.461+3295T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 152,080 control chromosomes in the GnomAD database, including 55,881 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 0.86 (55881 hom., cov: 32)
• Consequence: GABRB1 NM_000812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306
• Publications: 6 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.907 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB1	NM_000812.4	MANE Select	c.461+3295T>G		intron	N/A	NP_000803.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB1	ENST00000295454.8	TSL:1 MANE Select	c.461+3295T>G		intron	N/A	ENSP00000295454.3
	GABRB1	ENST00000510909.1	TSL:4	n.*129+3295T>G		intron	N/A	ENSP00000426766.1

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130193 AN: 151962 Hom.: 55849 Cov.: 32

Gnomad AFR AF: 0.915

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.872

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.875

Gnomad FIN AF: 0.789

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.869

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

GnomAD4 genome AF: 0.857 AC: 130282 AN: 152080 Hom.: 55881 Cov.: 32 AF XY: 0.856 AC XY: 63603 AN XY: 74310

African (AFR) AF: 0.915 AC: 37988 AN: 41518

American (AMR) AF: 0.856 AC: 13051 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.872 AC: 3023 AN: 3468

East Asian (EAS) AF: 0.831 AC: 4289 AN: 5160

South Asian (SAS) AF: 0.874 AC: 4212 AN: 4818

European-Finnish (FIN) AF: 0.789 AC: 8351 AN: 10588

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.831 AC: 56504 AN: 67964

Other (OTH) AF: 0.867 AC: 1835 AN: 2116

Alfa AF: 0.845 Hom.: 72530

Bravo AF: 0.863

Asia WGS AF: 0.855 AC: 2974 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.17
DANN	Benign	0.43
PhyloP100		-0.31
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: rs989808; hg19: chr4-47166781;