chr4-47376678-G-T

Variant names:

• chr4-47376678-G-T
• rs13107066
• NM_000812.4:c.545-26640G>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.545-26640G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 151,840 control chromosomes in the GnomAD database, including 21,904 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 0.53 (21904 hom., cov: 31)
• Consequence: GABRB1 NM_000812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.574 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.545-26640G>T		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.545-26640G>T		intron	N/A	ENSP00000295454.3	P18505-1
	GABRB1	ENST00000510909.1	TSL:4	n.*213-26640G>T		intron	N/A	ENSP00000426766.1	P18505-2

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80683 AN: 151722 Hom.: 21897 Cov.: 31

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.532 AC: 80716 AN: 151840 Hom.: 21904 Cov.: 31 AF XY: 0.524 AC XY: 38888 AN XY: 74234

African (AFR) AF: 0.539 AC: 22321 AN: 41400

American (AMR) AF: 0.456 AC: 6958 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 1999 AN: 3466

East Asian (EAS) AF: 0.184 AC: 947 AN: 5152

South Asian (SAS) AF: 0.482 AC: 2322 AN: 4816

European-Finnish (FIN) AF: 0.484 AC: 5103 AN: 10544

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39292 AN: 67888

Other (OTH) AF: 0.556 AC: 1174 AN: 2110

Alfa AF: 0.556 Hom.: 4714

Bravo AF: 0.529

Asia WGS AF: 0.356 AC: 1242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.38
DANN	Benign	0.86
PhyloP100		0.046
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: rs13107066; hg19: chr4-47378695;