rs2236781

Variant names:

• chr4-47033070-G-A
• rs2236781
• NM_000812.4:c.240+586G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-47033070-G-A
• chr4-47033070-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000812.4(GABRB1):​c.240+586G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GABRB1 NM_000812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950
• Publications: 5 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

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.240+586G>A		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.240+586G>A		intron	N/A	ENSP00000295454.3
	GABRB1	ENST00000509366.5	TSL:1	n.341+586G>A		intron	N/A
	GABRB1	ENST00000513567.5	TSL:4	c.141+586G>A		intron	N/A	ENSP00000426753.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 99002 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 51518

African (AFR) AF: 0.00 AC: 0 AN: 3746

American (AMR) AF: 0.00 AC: 0 AN: 6024

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2364

East Asian (EAS) AF: 0.00 AC: 0 AN: 5402

South Asian (SAS) AF: 0.00 AC: 0 AN: 15404

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4702

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 346

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 55736

Other (OTH) AF: 0.00 AC: 0 AN: 5278

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 2292

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.8
DANN	Benign	0.62
PhyloP100		-0.095

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: rs2236781; hg19: chr4-47035087;