chr4-47143090-C-T

Variant names:

• chr4-47143090-C-T
• rs7680321
• NM_000812.4:c.241-18159C>T

Variant summary

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

The NM_000812.4(GABRB1):​c.241-18159C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.9 in 151,768 control chromosomes in the GnomAD database, including 61,521 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 0.90 (61521 hom., cov: 30)
• Consequence: GABRB1 NM_000812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.530
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000812.4. 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
	GABRB1	NM_000812.4	MANE Select	c.241-18159C>T		intron	N/A	NP_000803.2	X5DNL6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB1	ENST00000295454.8	TSL:1 MANE Select	c.241-18159C>T		intron	N/A	ENSP00000295454.3	P18505-1
	GABRB1	ENST00000513567.5	TSL:4	c.142-18159C>T		intron	N/A	ENSP00000426753.1	D6REM0
	GABRB1	ENST00000510909.1	TSL:4	n.173-18159C>T		intron	N/A	ENSP00000426766.1	P18505-2

Frequencies

GnomAD3 genomes AF: 0.900 AC: 136471 AN: 151650 Hom.: 61475 Cov.: 30

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.987

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.902

Gnomad EAS AF: 0.804

Gnomad SAS AF: 0.933

Gnomad FIN AF: 0.930

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.905

Gnomad OTH AF: 0.895

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

GnomAD4 genome AF: 0.900 AC: 136573 AN: 151768 Hom.: 61521 Cov.: 30 AF XY: 0.903 AC XY: 66941 AN XY: 74160

African (AFR) AF: 0.888 AC: 36830 AN: 41456

American (AMR) AF: 0.903 AC: 13723 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.902 AC: 3128 AN: 3468

East Asian (EAS) AF: 0.804 AC: 4107 AN: 5108

South Asian (SAS) AF: 0.933 AC: 4493 AN: 4814

European-Finnish (FIN) AF: 0.930 AC: 9847 AN: 10584

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.905 AC: 61406 AN: 67834

Other (OTH) AF: 0.891 AC: 1878 AN: 2108

Alfa AF: 0.907 Hom.: 18112

Bravo AF: 0.895

Asia WGS AF: 0.868 AC: 3021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.2
DANN	Benign	0.47
PhyloP100		0.53
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7680321; hg19: chr4-47145107;