chr4-47162193-C-T

Variant names:

• chr4-47162193-C-T
• rs2119780
• NM_000812.4:c.461+724C>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.461+724C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.989 in 152,184 control chromosomes in the GnomAD database, including 74,509 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 0.99 (74509 hom., cov: 32)
• Consequence: GABRB1 NM_000812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31
• Publications: 1 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB1	NM_000812.4	c.461+724C>T		intron_variant	Intron 4 of 8	ENST00000295454.8	NP_000803.2
GABRB1	XM_024453976.2	c.362+724C>T		intron_variant	Intron 4 of 8		XP_024309744.1
GABRB1	XM_024453977.2	c.362+724C>T		intron_variant	Intron 5 of 9		XP_024309745.1
GABRB1	XM_017007986.3	c.461+724C>T		intron_variant	Intron 4 of 4		XP_016863475.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB1	ENST00000295454.8	c.461+724C>T		intron_variant	Intron 4 of 8	1	NM_000812.4	ENSP00000295454.3
GABRB1	ENST00000510909.1	n.*129+724C>T		intron_variant	Intron 3 of 4	4		ENSP00000426766.1

Frequencies

GnomAD3 genomes AF: 0.989 AC: 150458 AN: 152066 Hom.: 74452 Cov.: 32

Gnomad AFR AF: 0.963

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.997

Gnomad ASJ AF: 0.995

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.991

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

GnomAD4 genome AF: 0.989 AC: 150574 AN: 152184 Hom.: 74509 Cov.: 32 AF XY: 0.990 AC XY: 73637 AN XY: 74398

African (AFR) AF: 0.963 AC: 40016 AN: 41540

American (AMR) AF: 0.997 AC: 15196 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 3455 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5164 AN: 5164

South Asian (SAS) AF: 1.00 AC: 4826 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10624 AN: 10624

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 67995 AN: 68002

Other (OTH) AF: 0.991 AC: 2092 AN: 2110

Alfa AF: 0.995 Hom.: 27130

Bravo AF: 0.988

Asia WGS AF: 0.998 AC: 3464 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.088
DANN	Benign	0.36
PhyloP100		-2.3
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: rs2119780; hg19: chr4-47164210;