4-47161613-A-T

Position:

• chr4-47161613-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRB1	NM_000812.4	c.461+144A>T		intron_variant		ENST00000295454.8
GABRB1	XM_017007986.3	c.461+144A>T		intron_variant
GABRB1	XM_024453976.2	c.362+144A>T		intron_variant
GABRB1	XM_024453977.2	c.362+144A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRB1	ENST00000295454.8	c.461+144A>T		intron_variant		1	NM_000812.4	P1
GABRB1	ENST00000510909.1	c.*129+144A>T		intron_variant, NMD_transcript_variant		4

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

Gnomad4 AFR exome AF: 0.897

Gnomad4 AMR exome AF: 0.857

Gnomad4 ASJ exome AF: 0.882

Gnomad4 EAS exome AF: 0.852

Gnomad4 SAS exome AF: 0.890

Gnomad4 FIN exome AF: 0.823

Gnomad4 NFE exome AF: 0.845

Gnomad4 OTH exome AF: 0.851

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

Gnomad4 AFR AF: 0.901

Gnomad4 AMR AF: 0.858

Gnomad4 ASJ AF: 0.882

Gnomad4 EAS AF: 0.831

Gnomad4 SAS AF: 0.876

Gnomad4 FIN AF: 0.806

Gnomad4 NFE AF: 0.845

Gnomad4 OTH AF: 0.868

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.2
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs10016388; hg19: chr4-47163630;