rs4279178

Variant names:

• chr4-47066563-G-A
• rs4279178
• NM_000812.4:c.240+34079G>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.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
• Publications: 9 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=-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 rank	MANE	Protein	UniProt
GABRB1	NM_000812.4	c.240+34079G>A		intron_variant	Intron 3 of 8	ENST00000295454.8	NP_000803.2
GABRB1	XM_024453976.2	c.141+34079G>A		intron_variant	Intron 3 of 8		XP_024309744.1
GABRB1	XM_024453977.2	c.141+34079G>A		intron_variant	Intron 4 of 9		XP_024309745.1
GABRB1	XM_017007986.3	c.240+34079G>A		intron_variant	Intron 3 of 4		XP_016863475.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB1	ENST00000295454.8	c.240+34079G>A		intron_variant	Intron 3 of 8	1	NM_000812.4	ENSP00000295454.3
GABRB1	ENST00000513567.5	c.141+34079G>A		intron_variant	Intron 3 of 3	4		ENSP00000426753.1
GABRB1	ENST00000510909.1	n.172+34558G>A		intron_variant	Intron 2 of 4	4		ENSP00000426766.1

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

African (AFR) AF: 0.605 AC: 25072 AN: 41462

American (AMR) AF: 0.358 AC: 5466 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1530 AN: 3468

East Asian (EAS) AF: 0.514 AC: 2665 AN: 5186

South Asian (SAS) AF: 0.453 AC: 2180 AN: 4814

European-Finnish (FIN) AF: 0.455 AC: 4793 AN: 10524

Middle Eastern (MID) AF: 0.424 AC: 123 AN: 290

European-Non Finnish (NFE) AF: 0.482 AC: 32725 AN: 67944

Other (OTH) AF: 0.465 AC: 983 AN: 2114

Alfa AF: 0.487 Hom.: 8530

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
PhyloP100		-0.57
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: rs4279178; hg19: chr4-47068580;