NM_000812.4:c.545-8335T>C

Variant names:

• chr4-47394983-T-C
• rs7439087
• NM_000812.4:c.545-8335T>C

Variant summary

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

The NM_000812.4(GABRB1):​c.545-8335T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,044 control chromosomes in the GnomAD database, including 11,355 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 0.37 (11355 hom., cov: 32)
• Consequence: GABRB1 NM_000812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153
• Publications: 8 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000812.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB1	NM_000812.4	MANE Select	c.545-8335T>C		intron	N/A	NP_000803.2	X5DNL6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB1	ENST00000295454.8	TSL:1 MANE Select	c.545-8335T>C		intron	N/A	ENSP00000295454.3	P18505-1
	GABRB1	ENST00000510909.1	TSL:4	n.*213-8335T>C		intron	N/A	ENSP00000426766.1	P18505-2

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55892 AN: 151926 Hom.: 11320 Cov.: 32

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.368 AC: 55973 AN: 152044 Hom.: 11355 Cov.: 32 AF XY: 0.362 AC XY: 26924 AN XY: 74286

African (AFR) AF: 0.534 AC: 22142 AN: 41456

American (AMR) AF: 0.257 AC: 3929 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1059 AN: 3470

East Asian (EAS) AF: 0.149 AC: 770 AN: 5182

South Asian (SAS) AF: 0.319 AC: 1535 AN: 4812

European-Finnish (FIN) AF: 0.281 AC: 2963 AN: 10552

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22416 AN: 67976

Other (OTH) AF: 0.358 AC: 756 AN: 2110

Alfa AF: 0.328 Hom.: 11753

Bravo AF: 0.374

Asia WGS AF: 0.250 AC: 871 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.0
DANN	Benign	0.50
PhyloP100		0.15
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: rs7439087; hg19: chr4-47397000;