rs1372496

Variant names:

• chr4-47205791-T-C
• rs1372496
• NM_000812.4:c.461+44322T>C

Variant summary

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

The NM_000812.4(GABRB1):​c.461+44322T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.847 in 152,046 control chromosomes in the GnomAD database, including 54,467 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 0.85 (54467 hom., cov: 32)
• Consequence: GABRB1 NM_000812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225
• Publications: 3 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=-0.75).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB1	NM_000812.4	c.461+44322T>C		intron_variant	Intron 4 of 8	ENST00000295454.8	NP_000803.2
GABRB1	XM_024453976.2	c.362+44322T>C		intron_variant	Intron 4 of 8		XP_024309744.1
GABRB1	XM_024453977.2	c.362+44322T>C		intron_variant	Intron 5 of 9		XP_024309745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB1	ENST00000295454.8	c.461+44322T>C		intron_variant	Intron 4 of 8	1	NM_000812.4	ENSP00000295454.3
GABRB1	ENST00000510909.1	n.*129+44322T>C		intron_variant	Intron 3 of 4	4		ENSP00000426766.1

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128664 AN: 151928 Hom.: 54455 Cov.: 32

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.904

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.853

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.867

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

GnomAD4 genome AF: 0.847 AC: 128719 AN: 152046 Hom.: 54467 Cov.: 32 AF XY: 0.847 AC XY: 62950 AN XY: 74304

African (AFR) AF: 0.834 AC: 34608 AN: 41488

American (AMR) AF: 0.857 AC: 13067 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.904 AC: 3137 AN: 3472

East Asian (EAS) AF: 0.820 AC: 4237 AN: 5164

South Asian (SAS) AF: 0.852 AC: 4110 AN: 4824

European-Finnish (FIN) AF: 0.819 AC: 8668 AN: 10588

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.854 AC: 58031 AN: 67946

Other (OTH) AF: 0.865 AC: 1823 AN: 2108

Alfa AF: 0.844 Hom.: 7000

Bravo AF: 0.848

Asia WGS AF: 0.828 AC: 2877 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.6
DANN	Benign	0.79
PhyloP100		-0.23
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: rs1372496; hg19: chr4-47207808;