4-47384411-C-T

Variant names:

• chr4-47384411-C-T
• rs4376121
• NM_000812.4:c.545-18907C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000812.4(GABRB1):​c.545-18907C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0613 in 120,108 control chromosomes in the GnomAD database, including 459 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 0.061 (459 hom., cov: 31)
• Consequence: GABRB1 NM_000812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240
• Publications: 2 publications found

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]

GABRB1 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 45

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB1	NM_000812.4	c.545-18907C>T		intron_variant	Intron 5 of 8	ENST00000295454.8	NP_000803.2
GABRB1	XM_024453976.2	c.446-18907C>T		intron_variant	Intron 5 of 8		XP_024309744.1
GABRB1	XM_024453977.2	c.446-18907C>T		intron_variant	Intron 6 of 9		XP_024309745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB1	ENST00000295454.8	c.545-18907C>T		intron_variant	Intron 5 of 8	1	NM_000812.4	ENSP00000295454.3
GABRB1	ENST00000510909.1	n.*213-18907C>T		intron_variant	Intron 4 of 4	4		ENSP00000426766.1

Frequencies

GnomAD3 genomes AF: 0.0612 AC: 7346 AN: 120036 Hom.: 451 Cov.: 31

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0368

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.0825

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0424

Gnomad OTH AF: 0.0666

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

GnomAD4 genome AF: 0.0613 AC: 7367 AN: 120108 Hom.: 459 Cov.: 31 AF XY: 0.0684 AC XY: 3961 AN XY: 57926

African (AFR) AF: 0.0126 AC: 379 AN: 30132

American (AMR) AF: 0.137 AC: 1801 AN: 13132

Ashkenazi Jewish (ASJ) AF: 0.0368 AC: 114 AN: 3094

East Asian (EAS) AF: 0.295 AC: 1458 AN: 4938

South Asian (SAS) AF: 0.147 AC: 564 AN: 3824

European-Finnish (FIN) AF: 0.0825 AC: 534 AN: 6470

Middle Eastern (MID) AF: 0.107 AC: 28 AN: 262

European-Non Finnish (NFE) AF: 0.0424 AC: 2367 AN: 55818

Other (OTH) AF: 0.0724 AC: 122 AN: 1686

Alfa AF: 0.0145 Hom.: 9

Bravo AF: 0.0532

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.3
DANN	Benign	0.65
PhyloP100		-0.024
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4376121; hg19: chr4-47386428;