rs10028945

Variant names:

• chr4-47426288-G-A
• rs10028945
• NM_000812.4:c.*270G>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.*270G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 276,588 control chromosomes in the GnomAD database, including 7,820 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 0.23 (4279 hom., cov: 31)
  • Exomes 𝑓: 0.23 (3541 hom.)
• Consequence: GABRB1 NM_000812.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380
• Publications: 14 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.246 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.*270G>A		3_prime_UTR	Exon 9 of 9	NP_000803.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB1	ENST00000295454.8	TSL:1 MANE Select	c.*270G>A		3_prime_UTR	Exon 9 of 9	ENSP00000295454.3

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35455 AN: 151812 Hom.: 4273 Cov.: 31

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.237

GnomAD4 exome AF: 0.235 AC: 29286 AN: 124658 Hom.: 3541 Cov.: 0 AF XY: 0.238 AC XY: 14882 AN XY: 62630

African (AFR) AF: 0.254 AC: 1137 AN: 4478

American (AMR) AF: 0.166 AC: 704 AN: 4234

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 1216 AN: 5340

East Asian (EAS) AF: 0.109 AC: 1174 AN: 10782

South Asian (SAS) AF: 0.185 AC: 408 AN: 2204

European-Finnish (FIN) AF: 0.239 AC: 1612 AN: 6732

Middle Eastern (MID) AF: 0.237 AC: 170 AN: 716

European-Non Finnish (NFE) AF: 0.253 AC: 20581 AN: 81266

Other (OTH) AF: 0.256 AC: 2284 AN: 8906

GnomAD4 genome AF: 0.234 AC: 35476 AN: 151930 Hom.: 4279 Cov.: 31 AF XY: 0.231 AC XY: 17177 AN XY: 74246

African (AFR) AF: 0.244 AC: 10126 AN: 41440

American (AMR) AF: 0.187 AC: 2855 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 710 AN: 3468

East Asian (EAS) AF: 0.130 AC: 675 AN: 5178

South Asian (SAS) AF: 0.180 AC: 866 AN: 4808

European-Finnish (FIN) AF: 0.244 AC: 2558 AN: 10504

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.249 AC: 16923 AN: 67940

Other (OTH) AF: 0.234 AC: 492 AN: 2102

Alfa AF: 0.244 Hom.: 5969

Bravo AF: 0.231

Asia WGS AF: 0.161 AC: 558 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.5
DANN	Benign	0.63
PhyloP100		0.038
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: rs10028945; hg19: chr4-47428305;