rs4315750

Variant names:

• chr4-47049168-A-C
• rs4315750
• NM_000812.4:c.240+16684A>C

Your query was ambiguous. Multiple possible variants found:

• chr4-47049168-A-C
• chr4-47049168-A-G
• chr4-47049168-A-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.240+16684A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 152,088 control chromosomes in the GnomAD database, including 58,968 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 0.88 (58968 hom., cov: 31)
• Consequence: GABRB1 NM_000812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.960
• Publications: 10 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000812.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB1	NM_000812.4	MANE Select	c.240+16684A>C		intron	N/A	NP_000803.2	X5DNL6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB1	ENST00000295454.8	TSL:1 MANE Select	c.240+16684A>C		intron	N/A	ENSP00000295454.3	P18505-1
	GABRB1	ENST00000513567.5	TSL:4	c.141+16684A>C		intron	N/A	ENSP00000426753.1	D6REM0
	GABRB1	ENST00000510909.1	TSL:4	n.172+17163A>C		intron	N/A	ENSP00000426766.1	P18505-2

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133390 AN: 151970 Hom.: 58939 Cov.: 31

Gnomad AFR AF: 0.771

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.926

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.943

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.925

Gnomad OTH AF: 0.891

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

GnomAD4 genome AF: 0.878 AC: 133472 AN: 152088 Hom.: 58968 Cov.: 31 AF XY: 0.880 AC XY: 65452 AN XY: 74344

African (AFR) AF: 0.771 AC: 31946 AN: 41454

American (AMR) AF: 0.903 AC: 13788 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.926 AC: 3214 AN: 3470

East Asian (EAS) AF: 0.806 AC: 4165 AN: 5166

South Asian (SAS) AF: 0.919 AC: 4428 AN: 4820

European-Finnish (FIN) AF: 0.943 AC: 9987 AN: 10590

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

European-Non Finnish (NFE) AF: 0.925 AC: 62884 AN: 68004

Other (OTH) AF: 0.890 AC: 1881 AN: 2114

Alfa AF: 0.908 Hom.: 83457

Bravo AF: 0.868

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.59
PhyloP100		-0.96
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: rs4315750; hg19: chr4-47051185;