rs13139021

chr4-47004382-T-Cchr4-47004382-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRB1	XM_024453976.2	c.-20+10422T>C		intron_variant
GABRB1	XM_024453977.2	c.-20+9968T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRB1	ENST00000513567.5	c.-20+10456T>C		intron_variant		4

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

Gnomad4 AFR AF: 0.546

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.603

Gnomad4 EAS AF: 0.612

Gnomad4 SAS AF: 0.730

Gnomad4 FIN AF: 0.731

Gnomad4 NFE AF: 0.704

Gnomad4 OTH AF: 0.613

Alfa AF: 0.681 Hom.: 71967

Bravo AF: 0.607

Asia WGS AF: 0.657 AC: 2287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.95
Dann	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13139021; hg19: chr4-47006399;