4-47107343-A-G

Variant names:

• chr4-47107343-A-G
• rs1372491
• NM_000812.4:c.241-53906A>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.241-53906A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 151,832 control chromosomes in the GnomAD database, including 8,566 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 0.33 (8566 hom., cov: 32)
• Consequence: GABRB1 NM_000812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0670
• Publications: 3 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.351 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.241-53906A>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.241-53906A>G		intron	N/A	ENSP00000295454.3
	GABRB1	ENST00000513567.5	TSL:4	c.142-53906A>G		intron	N/A	ENSP00000426753.1
	GABRB1	ENST00000510909.1	TSL:4	n.173-53906A>G		intron	N/A	ENSP00000426766.1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 49996 AN: 151714 Hom.: 8557 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.0477

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.330 AC: 50036 AN: 151832 Hom.: 8566 Cov.: 32 AF XY: 0.329 AC XY: 24432 AN XY: 74206

African (AFR) AF: 0.314 AC: 12990 AN: 41428

American (AMR) AF: 0.359 AC: 5457 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1532 AN: 3462

East Asian (EAS) AF: 0.0482 AC: 249 AN: 5166

South Asian (SAS) AF: 0.304 AC: 1463 AN: 4818

European-Finnish (FIN) AF: 0.330 AC: 3479 AN: 10556

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.349 AC: 23678 AN: 67870

Other (OTH) AF: 0.349 AC: 738 AN: 2112

Alfa AF: 0.351 Hom.: 15784

Bravo AF: 0.325

Asia WGS AF: 0.200 AC: 695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.6
DANN	Benign	0.62
PhyloP100		0.067
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: rs1372491; hg19: chr4-47109360;