rs2055940

Variant names:

• chr4-46995896-G-A
• rs2055940
• ENST00000513567.5:c.-20+1970G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-46995896-G-A
• chr4-46995896-G-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+1970G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 151,888 control chromosomes in the GnomAD database, including 4,976 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 0.24 (4976 hom., cov: 32)
• Consequence: GABRB1 ENST00000513567.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 6 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.318 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+1970G>A		intron	N/A	ENSP00000426753.1	D6REM0

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35985 AN: 151770 Hom.: 4974 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.237 AC: 35988 AN: 151888 Hom.: 4976 Cov.: 32 AF XY: 0.226 AC XY: 16815 AN XY: 74240

African (AFR) AF: 0.129 AC: 5359 AN: 41440

American (AMR) AF: 0.233 AC: 3563 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1150 AN: 3462

East Asian (EAS) AF: 0.152 AC: 786 AN: 5170

South Asian (SAS) AF: 0.113 AC: 546 AN: 4818

European-Finnish (FIN) AF: 0.174 AC: 1824 AN: 10506

Middle Eastern (MID) AF: 0.322 AC: 94 AN: 292

European-Non Finnish (NFE) AF: 0.321 AC: 21809 AN: 67918

Other (OTH) AF: 0.271 AC: 571 AN: 2108

Alfa AF: 0.292 Hom.: 8004

Bravo AF: 0.239

Asia WGS AF: 0.121 AC: 421 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.99
DANN	Benign	0.21
PhyloP100		-1.0

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: rs2055940;

hg19: chr4-46997913;