chr4-46113962-G-A

Variant names:

• chr4-46113962-G-A
• rs6813633
• NM_173536.4:c.104+9848C>T

Variant summary

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

The NM_173536.4(GABRG1):​c.104+9848C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 150,740 control chromosomes in the GnomAD database, including 24,924 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 0.56 (24924 hom., cov: 31)
• Consequence: GABRG1 NM_173536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192
• Publications: 3 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173536.4. 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
	GABRG1	NM_173536.4	MANE Select	c.104+9848C>T		intron	N/A	NP_775807.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG1	ENST00000295452.5	TSL:1 MANE Select	c.104+9848C>T		intron	N/A	ENSP00000295452.4	Q8N1C3
	GABRG1	ENST00000964875.1		c.104+9848C>T		intron	N/A	ENSP00000634934.1

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84086 AN: 150622 Hom.: 24879 Cov.: 31

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.558 AC: 84188 AN: 150740 Hom.: 24924 Cov.: 31 AF XY: 0.549 AC XY: 40415 AN XY: 73582

African (AFR) AF: 0.752 AC: 31095 AN: 41326

American (AMR) AF: 0.469 AC: 7072 AN: 15066

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1306 AN: 3430

East Asian (EAS) AF: 0.361 AC: 1837 AN: 5088

South Asian (SAS) AF: 0.317 AC: 1523 AN: 4810

European-Finnish (FIN) AF: 0.492 AC: 5190 AN: 10542

Middle Eastern (MID) AF: 0.370 AC: 108 AN: 292

European-Non Finnish (NFE) AF: 0.514 AC: 34551 AN: 67186

Other (OTH) AF: 0.517 AC: 1081 AN: 2090

Alfa AF: 0.538 Hom.: 2953

Bravo AF: 0.569

Asia WGS AF: 0.375 AC: 1304 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.55
DANN	Benign	0.42
PhyloP100		-0.19
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: rs6813633; hg19: chr4-46115979;