chr4-47106640-G-C

Variant names:

• chr4-47106640-G-C
• rs9291303
• NM_000812.4:c.241-54609G>C

Variant summary

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

The NM_000812.4(GABRB1):​c.241-54609G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0665 in 151,860 control chromosomes in the GnomAD database, including 865 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 0.067 (865 hom., cov: 32)
• Consequence: GABRB1 NM_000812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.819
• Publications: 0 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 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.241-54609G>C		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.241-54609G>C		intron	N/A	ENSP00000295454.3
	GABRB1	ENST00000513567.5	TSL:4	c.142-54609G>C		intron	N/A	ENSP00000426753.1
	GABRB1	ENST00000510909.1	TSL:4	n.173-54609G>C		intron	N/A	ENSP00000426766.1

Frequencies

GnomAD3 genomes AF: 0.0665 AC: 10086 AN: 151742 Hom.: 862 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0229

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.0244

Gnomad SAS AF: 0.0595

Gnomad FIN AF: 0.0520

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00711

Gnomad OTH AF: 0.0531

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

GnomAD4 genome AF: 0.0665 AC: 10102 AN: 151860 Hom.: 865 Cov.: 32 AF XY: 0.0679 AC XY: 5044 AN XY: 74248

African (AFR) AF: 0.196 AC: 8105 AN: 41350

American (AMR) AF: 0.0228 AC: 348 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.0245 AC: 85 AN: 3468

East Asian (EAS) AF: 0.0246 AC: 127 AN: 5154

South Asian (SAS) AF: 0.0589 AC: 283 AN: 4804

European-Finnish (FIN) AF: 0.0520 AC: 551 AN: 10586

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00713 AC: 484 AN: 67928

Other (OTH) AF: 0.0525 AC: 111 AN: 2114

Alfa AF: 0.0425 Hom.: 61

Bravo AF: 0.0674

Asia WGS AF: 0.0640 AC: 223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.29
DANN	Benign	0.42
PhyloP100		-0.82
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: rs9291303; hg19: chr4-47108657;