chr4-47004382-T-C

Variant names:

• chr4-47004382-T-C
• rs13139021
• ENST00000513567.5:c.-20+10456T>C

Variant summary

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

The ENST00000513567.5(GABRB1):​c.-20+10456T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 152,050 control chromosomes in the GnomAD database, including 31,380 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 (31380 hom., cov: 33)
• Consequence: GABRB1 ENST00000513567.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.152
• Publications: 8 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)
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000513567.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB1	ENST00000513567.5	TSL:4	c.-20+10456T>C		intron	N/A	ENSP00000426753.1	D6REM0

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96671 AN: 151932 Hom.: 31380 Cov.: 33

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.731

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.615

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

GnomAD4 genome AF: 0.636 AC: 96686 AN: 152050 Hom.: 31380 Cov.: 33 AF XY: 0.638 AC XY: 47428 AN XY: 74340

African (AFR) AF: 0.546 AC: 22619 AN: 41448

American (AMR) AF: 0.497 AC: 7589 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2091 AN: 3468

East Asian (EAS) AF: 0.612 AC: 3172 AN: 5182

South Asian (SAS) AF: 0.730 AC: 3514 AN: 4812

European-Finnish (FIN) AF: 0.731 AC: 7716 AN: 10560

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.704 AC: 47867 AN: 67984

Other (OTH) AF: 0.613 AC: 1297 AN: 2116

Alfa AF: 0.672 Hom.: 118162

Bravo AF: 0.607

Asia WGS AF: 0.657 AC: 2287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.95
DANN	Benign	0.39
PhyloP100		0.15

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13139021; hg19: chr4-47006399;