4-47033070-G-C

Position:

• chr4-47033070-G-C

Variant summary

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

The NM_000812.4(GABRB1):​c.240+586G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 250,642 control chromosomes in the GnomAD database, including 31,413 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 0.49 (18530 hom., cov: 33)
  • Exomes 𝑓: 0.52 (12883 hom.)
• Consequence: GABRB1 NM_000812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRB1	NM_000812.4	c.240+586G>C		intron_variant		ENST00000295454.8	NP_000803.2
GABRB1	XM_017007986.3	c.240+586G>C		intron_variant			XP_016863475.1
GABRB1	XM_024453976.2	c.141+586G>C		intron_variant			XP_024309744.1
GABRB1	XM_024453977.2	c.141+586G>C		intron_variant			XP_024309745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRB1	ENST00000295454.8	c.240+586G>C		intron_variant		1	NM_000812.4	ENSP00000295454	P1
GABRB1	ENST00000509366.5	n.341+586G>C		intron_variant, non_coding_transcript_variant		1
GABRB1	ENST00000513567.5	c.141+586G>C		intron_variant		4		ENSP00000426753
GABRB1	ENST00000510909.1	c.172+1065G>C		intron_variant, NMD_transcript_variant		4		ENSP00000426766

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74931 AN: 151994 Hom.: 18529 Cov.: 33

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.470

GnomAD4 exome AF: 0.517 AC: 50966 AN: 98530 Hom.: 12883 AF XY: 0.517 AC XY: 26525 AN XY: 51278

Gnomad4 AFR exome AF: 0.483

Gnomad4 AMR exome AF: 0.470

Gnomad4 ASJ exome AF: 0.444

Gnomad4 EAS exome AF: 0.545

Gnomad4 SAS exome AF: 0.521

Gnomad4 FIN exome AF: 0.519

Gnomad4 NFE exome AF: 0.525

Gnomad4 OTH exome AF: 0.508

GnomAD4 genome AF: 0.493 AC: 74954 AN: 152112 Hom.: 18530 Cov.: 33 AF XY: 0.493 AC XY: 36674 AN XY: 74352

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.494

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.468

Alfa AF: 0.500 Hom.: 2292

Bravo AF: 0.486

Asia WGS AF: 0.497 AC: 1727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.4
DANN	Benign	0.49

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: rs2236781; hg19: chr4-47035087;