rs1372497

Positions:

• chr4-47220321-T-C

Variant summary

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

The NM_000812.4(GABRB1):​c.461+58852T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,744 control chromosomes in the GnomAD database, including 8,833 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 0.34 (8833 hom., cov: 32)
• Consequence: GABRB1 NM_000812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.356

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRB1	NM_000812.4	c.461+58852T>C		intron_variant		ENST00000295454.8	NP_000803.2
GABRB1	XM_024453976.2	c.362+58852T>C		intron_variant			XP_024309744.1
GABRB1	XM_024453977.2	c.362+58852T>C		intron_variant			XP_024309745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRB1	ENST00000295454.8	c.461+58852T>C		intron_variant		1	NM_000812.4	ENSP00000295454	P1
GABRB1	ENST00000510909.1	c.*129+58852T>C		intron_variant, NMD_transcript_variant		4		ENSP00000426766

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50809 AN: 151626 Hom.: 8820 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.335 AC: 50853 AN: 151744 Hom.: 8833 Cov.: 32 AF XY: 0.338 AC XY: 25032 AN XY: 74154

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.497

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.314

Alfa AF: 0.328 Hom.: 11422

Bravo AF: 0.317

Asia WGS AF: 0.245 AC: 852 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.8
DANN	Benign	0.74

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: rs1372497; hg19: chr4-47222338;