rs3934674

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr4-47011121-A-G
• chr4-47011121-A-T

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)
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.772 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+17195A>G		intron	N/A	ENSP00000426753.1	D6REM0

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3934674;

hg19: chr4-47013138;