rs1566857

Variant names:

• chr4-46046863-A-T
• rs1566857
• NM_173536.4:c.1131+4561T>A

Variant summary

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

The NM_173536.4(GABRG1):​c.1131+4561T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0315 in 152,214 control chromosomes in the GnomAD database, including 176 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 0.031 (176 hom., cov: 32)
• Consequence: GABRG1 NM_173536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390
• Publications: 2 publications found

Genes affected

GABRG1 (HGNC:4086): (gamma-aminobutyric acid type A receptor subunit gamma1) The protein encoded by this gene belongs to the ligand-gated ionic channel family. It is an integral membrane protein and plays an important role in inhibiting neurotransmission by binding to the benzodiazepine receptor and opening an integral chloride channel. This gene is clustered with three other family members on chromosome 4. [provided by RefSeq, Jul 2008]

GABRG1 Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG1	NM_173536.4	c.1131+4561T>A		intron_variant	Intron 8 of 8	ENST00000295452.5	NP_775807.2
GABRG1	XM_017007990.2	c.744+4561T>A		intron_variant	Intron 6 of 6		XP_016863479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG1	ENST00000295452.5	c.1131+4561T>A		intron_variant	Intron 8 of 8	1	NM_173536.4	ENSP00000295452.4

Frequencies

GnomAD3 genomes AF: 0.0316 AC: 4799 AN: 152096 Hom.: 176 Cov.: 32

Gnomad AFR AF: 0.00589

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0645

Gnomad ASJ AF: 0.0282

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.0252

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.0241

Gnomad OTH AF: 0.0344

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

GnomAD4 genome AF: 0.0315 AC: 4792 AN: 152214 Hom.: 176 Cov.: 32 AF XY: 0.0357 AC XY: 2660 AN XY: 74406

African (AFR) AF: 0.00587 AC: 244 AN: 41570

American (AMR) AF: 0.0645 AC: 984 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0282 AC: 98 AN: 3470

East Asian (EAS) AF: 0.114 AC: 585 AN: 5154

South Asian (SAS) AF: 0.180 AC: 867 AN: 4816

European-Finnish (FIN) AF: 0.0252 AC: 268 AN: 10618

Middle Eastern (MID) AF: 0.0514 AC: 15 AN: 292

European-Non Finnish (NFE) AF: 0.0241 AC: 1642 AN: 68008

Other (OTH) AF: 0.0341 AC: 72 AN: 2114

Alfa AF: 0.0294 Hom.: 4

Bravo AF: 0.0305

Asia WGS AF: 0.126 AC: 437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.59
PhyloP100		0.039
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: rs1566857; hg19: chr4-46048880;