chr4-47376678-G-T

Position:

• chr4-47376678-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000812.4(GABRB1):​c.545-26640G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 151,840 control chromosomes in the GnomAD database, including 21,904 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 0.53 (21904 hom., cov: 31)
• Consequence: GABRB1 NM_000812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRB1	NM_000812.4	c.545-26640G>T		intron_variant		ENST00000295454.8
GABRB1	XM_024453976.2	c.446-26640G>T		intron_variant
GABRB1	XM_024453977.2	c.446-26640G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRB1	ENST00000295454.8	c.545-26640G>T		intron_variant		1	NM_000812.4	P1
GABRB1	ENST00000510909.1	c.*213-26640G>T		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80683 AN: 151722 Hom.: 21897 Cov.: 31

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.532 AC: 80716 AN: 151840 Hom.: 21904 Cov.: 31 AF XY: 0.524 AC XY: 38888 AN XY: 74234

Gnomad4 AFR AF: 0.539

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.577

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.556

Alfa AF: 0.556 Hom.: 4714

Bravo AF: 0.529

Asia WGS AF: 0.356 AC: 1242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.38
DANN	Benign	0.86

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: rs13107066; hg19: chr4-47378695;