ENST00000513567.5:c.-20+10456T>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)

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB1	XM_024453976.2	c.-20+10422T>C		intron_variant	Intron 1 of 8		XP_024309744.1
GABRB1	XM_024453977.2	c.-20+9968T>C		intron_variant	Intron 2 of 9		XP_024309745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB1	ENST00000513567.5	c.-20+10456T>C		intron_variant	Intron 1 of 3	4		ENSP00000426753.1

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 v4.3

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;