chr4-47141348-G-T

Variant names:

• chr4-47141348-G-T
• rs2351299
• NM_000812.4:c.241-19901G>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.241-19901G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 151,740 control chromosomes in the GnomAD database, including 2,979 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 0.19 (2979 hom., cov: 32)
• Consequence: GABRB1 NM_000812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.232
• Publications: 9 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB1	NM_000812.4	c.241-19901G>T		intron_variant	Intron 3 of 8	ENST00000295454.8	NP_000803.2
GABRB1	XM_024453976.2	c.142-19901G>T		intron_variant	Intron 3 of 8		XP_024309744.1
GABRB1	XM_024453977.2	c.142-19901G>T		intron_variant	Intron 4 of 9		XP_024309745.1
GABRB1	XM_017007986.3	c.241-19901G>T		intron_variant	Intron 3 of 4		XP_016863475.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB1	ENST00000295454.8	c.241-19901G>T		intron_variant	Intron 3 of 8	1	NM_000812.4	ENSP00000295454.3
GABRB1	ENST00000513567.5	c.142-19901G>T		intron_variant	Intron 3 of 3	4		ENSP00000426753.1
GABRB1	ENST00000510909.1	n.173-19901G>T		intron_variant	Intron 2 of 4	4		ENSP00000426766.1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28995 AN: 151622 Hom.: 2978 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.191 AC: 29004 AN: 151740 Hom.: 2979 Cov.: 32 AF XY: 0.192 AC XY: 14222 AN XY: 74154

African (AFR) AF: 0.245 AC: 10149 AN: 41434

American (AMR) AF: 0.123 AC: 1870 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 353 AN: 3462

East Asian (EAS) AF: 0.330 AC: 1698 AN: 5138

South Asian (SAS) AF: 0.171 AC: 827 AN: 4824

European-Finnish (FIN) AF: 0.184 AC: 1937 AN: 10554

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11596 AN: 67836

Other (OTH) AF: 0.163 AC: 342 AN: 2100

Alfa AF: 0.168 Hom.: 2757

Bravo AF: 0.187

Asia WGS AF: 0.234 AC: 812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.47
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: rs2351299; hg19: chr4-47143365;