4-47345272-A-G

Variant names:

• chr4-47345272-A-G
• rs7665508
• NM_000812.4:c.544+25063A>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+25063A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 152,024 control chromosomes in the GnomAD database, including 11,012 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 0.38 (11012 hom., cov: 32)
• Consequence: GABRB1 NM_000812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.580
• Publications: 1 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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.446 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.544+25063A>G		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.544+25063A>G		intron	N/A	ENSP00000295454.3
	GABRB1	ENST00000510909.1	TSL:4	n.*212+25063A>G		intron	N/A	ENSP00000426766.1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57573 AN: 151906 Hom.: 10997 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.379 AC: 57626 AN: 152024 Hom.: 11012 Cov.: 32 AF XY: 0.375 AC XY: 27851 AN XY: 74310

African (AFR) AF: 0.334 AC: 13844 AN: 41472

American (AMR) AF: 0.400 AC: 6108 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1511 AN: 3470

East Asian (EAS) AF: 0.297 AC: 1529 AN: 5152

South Asian (SAS) AF: 0.462 AC: 2221 AN: 4808

European-Finnish (FIN) AF: 0.270 AC: 2843 AN: 10548

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28124 AN: 67984

Other (OTH) AF: 0.403 AC: 849 AN: 2108

Alfa AF: 0.402 Hom.: 37682

Bravo AF: 0.383

Asia WGS AF: 0.363 AC: 1261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.22
DANN	Benign	0.43
PhyloP100		-0.58
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: rs7665508; hg19: chr4-47347289;