rs6284

chr4-47320202-C-Achr4-47320202-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_000812.4(GABRB1):c.537C>A(p.Ile179=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,579,056 control chromosomes in the GnomAD database, including 29,642 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2389 hom., cov: 32)
  • Exomes 𝑓: 0.19 (27253 hom.)
• Consequence: GABRB1 NM_000812.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0820

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP6: Variant 4-47320202-C-A is Benign according to our data. Variant chr4-47320202-C-A is described in ClinVar as [Benign]. Clinvar id is 1573985.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.082 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRB1	NM_000812.4	c.537C>A	p.Ile179=	synonymous_variant	5/9	ENST00000295454.8
GABRB1	XM_024453976.2	c.438C>A	p.Ile146=	synonymous_variant	5/9
GABRB1	XM_024453977.2	c.438C>A	p.Ile146=	synonymous_variant	6/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRB1	ENST00000295454.8	c.537C>A	p.Ile179=	synonymous_variant	5/9	1	NM_000812.4	P1
GABRB1	ENST00000510909.1	c.*205C>A		3_prime_UTR_variant, NMD_transcript_variant	4/5	4

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26172 AN: 152016 Hom.: 2392 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.163

GnomAD3 exomes AF: 0.170 AC: 42605 AN: 251052 Hom.: 4036 AF XY: 0.170 AC XY: 23073 AN XY: 135684

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.131

Gnomad ASJ exome AF: 0.128

Gnomad EAS exome AF: 0.108

Gnomad SAS exome AF: 0.105

Gnomad FIN exome AF: 0.259

Gnomad NFE exome AF: 0.202

Gnomad OTH exome AF: 0.173

GnomAD4 exome AF: 0.190 AC: 271421 AN: 1426922 Hom.: 27253 Cov.: 28 AF XY: 0.188 AC XY: 133974 AN XY: 712108

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.128

Gnomad4 EAS exome AF: 0.114

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.264

Gnomad4 NFE exome AF: 0.203

Gnomad4 OTH exome AF: 0.180

GnomAD4 genome AF: 0.172 AC: 26169 AN: 152134 Hom.: 2389 Cov.: 32 AF XY: 0.171 AC XY: 12724 AN XY: 74364

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.162

Alfa AF: 0.190 Hom.: 6505

Bravo AF: 0.158

Asia WGS AF: 0.124 AC: 433 AN: 3478

EpiCase AF: 0.194

EpiControl AF: 0.196

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
Cadd	Benign	6.9
Dann	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs6284; hg19: chr4-47322219; COSMIC: COSV55001820;