ENST00000513567.5:c.-20+17195A>G

Variant names:

• chr4-47011121-A-G
• rs3934674
• ENST00000513567.5:c.-20+17195A>G

Variant summary

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

The ENST00000513567.5(GABRB1):​c.-20+17195A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,104 control chromosomes in the GnomAD database, including 37,318 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 0.70 (37318 hom., cov: 32)
• Consequence: GABRB1 ENST00000513567.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.952
• Publications: 10 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB1	XM_024453976.2	c.-20+17161A>G		intron_variant	Intron 1 of 8		XP_024309744.1
GABRB1	XM_024453977.2	c.-20+16707A>G		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+17195A>G		intron_variant	Intron 1 of 3	4		ENSP00000426753.1

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106166 AN: 151986 Hom.: 37309 Cov.: 32

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.833

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.710

Gnomad OTH AF: 0.673

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

GnomAD4 genome AF: 0.698 AC: 106206 AN: 152104 Hom.: 37318 Cov.: 32 AF XY: 0.706 AC XY: 52474 AN XY: 74348

African (AFR) AF: 0.655 AC: 27171 AN: 41460

American (AMR) AF: 0.639 AC: 9764 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2209 AN: 3470

East Asian (EAS) AF: 0.747 AC: 3858 AN: 5162

South Asian (SAS) AF: 0.793 AC: 3822 AN: 4820

European-Finnish (FIN) AF: 0.833 AC: 8829 AN: 10598

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.710 AC: 48306 AN: 68004

Other (OTH) AF: 0.669 AC: 1415 AN: 2114

Alfa AF: 0.697 Hom.: 53152

Bravo AF: 0.680

Asia WGS AF: 0.751 AC: 2614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.1
DANN	Benign	0.66
PhyloP100		0.95

Splicing

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

Other links and lift over

dbSNP: rs3934674; hg19: chr4-47013138;