chr4-47033070-G-C

Variant names:

• chr4-47033070-G-C
• rs2236781
• NM_000812.4:c.240+586G>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.240+586G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 250,642 control chromosomes in the GnomAD database, including 31,413 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 0.49 (18530 hom., cov: 33)
  • Exomes 𝑓: 0.52 (12883 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.511 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.240+586G>C		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>C		intron	N/A	ENSP00000295454.3
	GABRB1	ENST00000509366.5	TSL:1	n.341+586G>C		intron	N/A
	GABRB1	ENST00000513567.5	TSL:4	c.141+586G>C		intron	N/A	ENSP00000426753.1

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74931 AN: 151994 Hom.: 18529 Cov.: 33

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.470

GnomAD4 exome AF: 0.517 AC: 50966 AN: 98530 Hom.: 12883 AF XY: 0.517 AC XY: 26525 AN XY: 51278

African (AFR) AF: 0.483 AC: 1806 AN: 3736

American (AMR) AF: 0.470 AC: 2821 AN: 5998

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1044 AN: 2354

East Asian (EAS) AF: 0.545 AC: 2926 AN: 5368

South Asian (SAS) AF: 0.521 AC: 7992 AN: 15328

European-Finnish (FIN) AF: 0.519 AC: 2435 AN: 4688

Middle Eastern (MID) AF: 0.477 AC: 165 AN: 346

European-Non Finnish (NFE) AF: 0.525 AC: 29110 AN: 55462

Other (OTH) AF: 0.508 AC: 2667 AN: 5250

GnomAD4 genome AF: 0.493 AC: 74954 AN: 152112 Hom.: 18530 Cov.: 33 AF XY: 0.493 AC XY: 36674 AN XY: 74352

African (AFR) AF: 0.486 AC: 20164 AN: 41498

American (AMR) AF: 0.450 AC: 6886 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1499 AN: 3470

East Asian (EAS) AF: 0.528 AC: 2719 AN: 5154

South Asian (SAS) AF: 0.494 AC: 2385 AN: 4830

European-Finnish (FIN) AF: 0.494 AC: 5223 AN: 10580

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.507 AC: 34475 AN: 67974

Other (OTH) AF: 0.468 AC: 990 AN: 2114

Alfa AF: 0.500 Hom.: 2292

Bravo AF: 0.486

Asia WGS AF: 0.497 AC: 1727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.4
DANN	Benign	0.49
PhyloP100		-0.095
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: rs2236781; hg19: chr4-47035087;