NM_000812.4:c.462-61806C>T

Variant names:

• chr4-47258321-C-T
• rs3114084
• NM_000812.4:c.462-61806C>T

Variant summary

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

The NM_000812.4(GABRB1):​c.462-61806C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 151,914 control chromosomes in the GnomAD database, including 31,465 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 0.64 (31465 hom., cov: 31)
• Consequence: GABRB1 NM_000812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 0 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.79 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB1	NM_000812.4	MANE Select	c.462-61806C>T		intron	N/A	NP_000803.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB1	ENST00000295454.8	TSL:1 MANE Select	c.462-61806C>T		intron	N/A	ENSP00000295454.3
	GABRB1	ENST00000510909.1	TSL:4	n.*130-61806C>T		intron	N/A	ENSP00000426766.1

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97157 AN: 151796 Hom.: 31441 Cov.: 31

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.765

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.671

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

GnomAD4 genome AF: 0.640 AC: 97200 AN: 151914 Hom.: 31465 Cov.: 31 AF XY: 0.637 AC XY: 47288 AN XY: 74250

African (AFR) AF: 0.580 AC: 24020 AN: 41442

American (AMR) AF: 0.704 AC: 10736 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.765 AC: 2654 AN: 3468

East Asian (EAS) AF: 0.744 AC: 3843 AN: 5164

South Asian (SAS) AF: 0.811 AC: 3902 AN: 4812

European-Finnish (FIN) AF: 0.503 AC: 5307 AN: 10546

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.654 AC: 44401 AN: 67914

Other (OTH) AF: 0.673 AC: 1422 AN: 2112

Alfa AF: 0.600 Hom.: 4037

Bravo AF: 0.652

Asia WGS AF: 0.743 AC: 2558 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.45
DANN	Benign	0.47
PhyloP100		-1.1
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: rs3114084; hg19: chr4-47260338;