rs10517179

chr4-47107059-C-T

Variant summary

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

The NM_000812.4(GABRB1):c.241-54190C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0631 in 152,090 control chromosomes in the GnomAD database, including 783 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 0.063 (783 hom., cov: 32)
• Consequence: GABRB1 NM_000812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRB1	NM_000812.4	c.241-54190C>T		intron_variant		ENST00000295454.8
GABRB1	XM_017007986.3	c.241-54190C>T		intron_variant
GABRB1	XM_024453976.2	c.142-54190C>T		intron_variant
GABRB1	XM_024453977.2	c.142-54190C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRB1	ENST00000295454.8	c.241-54190C>T		intron_variant		1	NM_000812.4	P1
GABRB1	ENST00000513567.5	c.142-54190C>T		intron_variant		4
GABRB1	ENST00000510909.1	c.173-54190C>T		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0632 AC: 9599 AN: 151972 Hom.: 782 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0194

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.0239

Gnomad SAS AF: 0.0588

Gnomad FIN AF: 0.0519

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00709

Gnomad OTH AF: 0.0502

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

GnomAD4 genome AF: 0.0631 AC: 9603 AN: 152090 Hom.: 783 Cov.: 32 AF XY: 0.0644 AC XY: 4789 AN XY: 74352

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.0193

Gnomad4 ASJ AF: 0.0245

Gnomad4 EAS AF: 0.0242

Gnomad4 SAS AF: 0.0583

Gnomad4 FIN AF: 0.0519

Gnomad4 NFE AF: 0.00711

Gnomad4 OTH AF: 0.0497

Alfa AF: 0.0299 Hom.: 91

Bravo AF: 0.0635

Asia WGS AF: 0.0620 AC: 216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.52
Dann	Benign	0.64

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: rs10517179; hg19: chr4-47109076;