rs3775534

Variant names:

• chr4-47320365-A-G
• rs3775534
• NM_000812.4:c.544+156A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000812.4(GABRB1):​c.544+156A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0679 in 152,278 control chromosomes in the GnomAD database, including 327 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 0.068 (327 hom., cov: 32)
• Consequence: GABRB1 NM_000812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362
• Publications: 4 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB1	NM_000812.4	c.544+156A>G		intron_variant	Intron 5 of 8	ENST00000295454.8	NP_000803.2
GABRB1	XM_024453976.2	c.445+156A>G		intron_variant	Intron 5 of 8		XP_024309744.1
GABRB1	XM_024453977.2	c.445+156A>G		intron_variant	Intron 6 of 9		XP_024309745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB1	ENST00000295454.8	c.544+156A>G		intron_variant	Intron 5 of 8	1	NM_000812.4	ENSP00000295454.3
GABRB1	ENST00000510909.1	n.*212+156A>G		intron_variant	Intron 4 of 4	4		ENSP00000426766.1

Frequencies

GnomAD3 genomes AF: 0.0679 AC: 10328 AN: 152160 Hom.: 326 Cov.: 32

Gnomad AFR AF: 0.0663

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0817

Gnomad ASJ AF: 0.0237

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.0130

Gnomad FIN AF: 0.0930

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0738

Gnomad OTH AF: 0.0641

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

GnomAD4 genome AF: 0.0679 AC: 10336 AN: 152278 Hom.: 327 Cov.: 32 AF XY: 0.0678 AC XY: 5047 AN XY: 74452

African (AFR) AF: 0.0663 AC: 2757 AN: 41562

American (AMR) AF: 0.0817 AC: 1249 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0237 AC: 82 AN: 3462

East Asian (EAS) AF: 0.00386 AC: 20 AN: 5186

South Asian (SAS) AF: 0.0122 AC: 59 AN: 4828

European-Finnish (FIN) AF: 0.0930 AC: 985 AN: 10594

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0739 AC: 5026 AN: 68032

Other (OTH) AF: 0.0639 AC: 135 AN: 2114

Alfa AF: 0.0698 Hom.: 776

Bravo AF: 0.0668

Asia WGS AF: 0.0210 AC: 74 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.0
DANN	Benign	0.82
PhyloP100		0.36
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: rs3775534; hg19: chr4-47322382; COSMIC: COSV54979317;