rs6287

Variant names:

• chr4-47406648-A-G
• rs6287
• NM_000812.4:c.836-34A>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.836-34A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,611,570 control chromosomes in the GnomAD database, including 11,854 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 0.12 (1094 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10760 hom.)
• Consequence: GABRB1 NM_000812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.467
• Publications: 7 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)
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 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.836-34A>G		intron	N/A	NP_000803.2	X5DNL6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB1	ENST00000295454.8	TSL:1 MANE Select	c.836-34A>G		intron	N/A	ENSP00000295454.3	P18505-1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17645 AN: 152130 Hom.: 1095 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0903

Gnomad ASJ AF: 0.0925

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.0957

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.110

GnomAD2 exomes AF: 0.105 AC: 26147 AN: 249870 AF XY: 0.105

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.0700

Gnomad ASJ exome AF: 0.0913

Gnomad EAS exome AF: 0.00288

Gnomad FIN exome AF: 0.133

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.122

GnomAD4 exome AF: 0.118 AC: 171912 AN: 1459322 Hom.: 10760 Cov.: 31 AF XY: 0.118 AC XY: 85334 AN XY: 725702

African (AFR) AF: 0.127 AC: 4241 AN: 33350

American (AMR) AF: 0.0726 AC: 3239 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.0891 AC: 2323 AN: 26060

East Asian (EAS) AF: 0.00502 AC: 199 AN: 39664

South Asian (SAS) AF: 0.101 AC: 8705 AN: 86162

European-Finnish (FIN) AF: 0.133 AC: 7073 AN: 53380

Middle Eastern (MID) AF: 0.126 AC: 728 AN: 5768

European-Non Finnish (NFE) AF: 0.125 AC: 138599 AN: 1110082

Other (OTH) AF: 0.113 AC: 6805 AN: 60254

GnomAD4 genome AF: 0.116 AC: 17649 AN: 152248 Hom.: 1094 Cov.: 32 AF XY: 0.113 AC XY: 8418 AN XY: 74444

African (AFR) AF: 0.129 AC: 5344 AN: 41534

American (AMR) AF: 0.0901 AC: 1379 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0925 AC: 321 AN: 3472

East Asian (EAS) AF: 0.00405 AC: 21 AN: 5190

South Asian (SAS) AF: 0.0958 AC: 462 AN: 4824

European-Finnish (FIN) AF: 0.126 AC: 1339 AN: 10602

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8492 AN: 68002

Other (OTH) AF: 0.111 AC: 234 AN: 2114

Alfa AF: 0.118 Hom.: 277

Bravo AF: 0.113

Asia WGS AF: 0.0530 AC: 185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.57
PhyloP100		-0.47
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: rs6287; hg19: chr4-47408665;