rs4279178

chr4-47066563-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.240+34079G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 151,982 control chromosomes in the GnomAD database, including 19,464 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 0.50 (19464 hom., cov: 33)
• Consequence: GABRB1 NM_000812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.567

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRB1	NM_000812.4	c.240+34079G>A		intron_variant		ENST00000295454.8
GABRB1	XM_017007986.3	c.240+34079G>A		intron_variant
GABRB1	XM_024453976.2	c.141+34079G>A		intron_variant
GABRB1	XM_024453977.2	c.141+34079G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRB1	ENST00000295454.8	c.240+34079G>A		intron_variant		1	NM_000812.4	P1
GABRB1	ENST00000513567.5	c.141+34079G>A		intron_variant		4
GABRB1	ENST00000510909.1	c.172+34558G>A		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75997 AN: 151864 Hom.: 19458 Cov.: 33

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.429

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.500 AC: 76031 AN: 151982 Hom.: 19464 Cov.: 33 AF XY: 0.495 AC XY: 36799 AN XY: 74294

Gnomad4 AFR AF: 0.605

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.465

Alfa AF: 0.484 Hom.: 4945

Bravo AF: 0.495

Asia WGS AF: 0.464 AC: 1615 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.93
Dann	Benign	0.37

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: rs4279178; hg19: chr4-47068580;