rs10028945

Positions:

• chr4-47426288-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRB1	NM_000812.4	c.*270G>A		3_prime_UTR_variant	9/9	ENST00000295454.8
GABRB1	XM_017007985.2	c.*270G>A		3_prime_UTR_variant	5/5
GABRB1	XM_024453976.2	c.*270G>A		3_prime_UTR_variant	9/9
GABRB1	XM_024453977.2	c.*270G>A		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRB1	ENST00000295454.8	c.*270G>A		3_prime_UTR_variant	9/9	1	NM_000812.4	P1

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

Gnomad4 AFR exome AF: 0.254

Gnomad4 AMR exome AF: 0.166

Gnomad4 ASJ exome AF: 0.228

Gnomad4 EAS exome AF: 0.109

Gnomad4 SAS exome AF: 0.185

Gnomad4 FIN exome AF: 0.239

Gnomad4 NFE exome AF: 0.253

Gnomad4 OTH exome AF: 0.256

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

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.234

Alfa AF: 0.245 Hom.: 4548

Bravo AF: 0.231

Asia WGS AF: 0.161 AC: 558 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.5
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs10028945; hg19: chr4-47428305;