4-47161613-A-T

Variant names:

• chr4-47161613-A-T
• rs10016388
• NM_000812.4:c.461+144A>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.461+144A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 628,956 control chromosomes in the GnomAD database, including 229,636 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 0.86 (56295 hom., cov: 31)
  • Exomes 𝑓: 0.85 (173341 hom.)
• Consequence: GABRB1 NM_000812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.251
• Publications: 0 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.893 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB1	NM_000812.4	MANE Select	c.461+144A>T		intron	N/A	NP_000803.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB1	ENST00000295454.8	TSL:1 MANE Select	c.461+144A>T		intron	N/A	ENSP00000295454.3
	GABRB1	ENST00000510909.1	TSL:4	n.*129+144A>T		intron	N/A	ENSP00000426766.1
	GABRB1	ENST00000513567.5	TSL:4	c.*153A>T		downstream_gene	N/A	ENSP00000426753.1

Frequencies

GnomAD3 genomes AF: 0.861 AC: 130702 AN: 151854 Hom.: 56267 Cov.: 31

Gnomad AFR AF: 0.901

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.882

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.870

GnomAD4 exome AF: 0.852 AC: 406314 AN: 476984 Hom.: 173341 AF XY: 0.854 AC XY: 214570 AN XY: 251144

African (AFR) AF: 0.897 AC: 11449 AN: 12758

American (AMR) AF: 0.857 AC: 15629 AN: 18230

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 12038 AN: 13648

East Asian (EAS) AF: 0.852 AC: 26376 AN: 30970

South Asian (SAS) AF: 0.890 AC: 40292 AN: 45256

European-Finnish (FIN) AF: 0.823 AC: 24975 AN: 30350

Middle Eastern (MID) AF: 0.889 AC: 1776 AN: 1998

European-Non Finnish (NFE) AF: 0.845 AC: 251128 AN: 297154

Other (OTH) AF: 0.851 AC: 22651 AN: 26620

GnomAD4 genome AF: 0.861 AC: 130786 AN: 151972 Hom.: 56295 Cov.: 31 AF XY: 0.860 AC XY: 63855 AN XY: 74270

African (AFR) AF: 0.901 AC: 37354 AN: 41480

American (AMR) AF: 0.858 AC: 13074 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 3060 AN: 3470

East Asian (EAS) AF: 0.831 AC: 4287 AN: 5156

South Asian (SAS) AF: 0.876 AC: 4221 AN: 4818

European-Finnish (FIN) AF: 0.806 AC: 8511 AN: 10554

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.845 AC: 57420 AN: 67950

Other (OTH) AF: 0.868 AC: 1829 AN: 2106

Alfa AF: 0.803 Hom.: 2801

Bravo AF: 0.865

Asia WGS AF: 0.854 AC: 2971 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.2
DANN	Benign	0.60
PhyloP100		0.25
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: rs10016388; hg19: chr4-47163630;