chr4-46116218-A-G

Variant names:

• chr4-46116218-A-G
• rs10938426
• NM_173536.4:c.104+7592T>C

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+7592T>C 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 150,468 control chromosomes in the GnomAD database, including 24,843 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 (24843 hom., cov: 32)
• Consequence: GABRG1 NM_173536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.693
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG1	NM_173536.4	c.104+7592T>C		intron_variant	Intron 1 of 8	ENST00000295452.5	NP_775807.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG1	ENST00000295452.5	c.104+7592T>C		intron_variant	Intron 1 of 8	1	NM_173536.4	ENSP00000295452.4

Frequencies

GnomAD3 genomes AF: 0.558 AC: 83888 AN: 150350 Hom.: 24798 Cov.: 32

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.517

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

GnomAD4 genome AF: 0.558 AC: 83990 AN: 150468 Hom.: 24843 Cov.: 32 AF XY: 0.549 AC XY: 40348 AN XY: 73502

African (AFR) AF: 0.752 AC: 31075 AN: 41342

American (AMR) AF: 0.469 AC: 7060 AN: 15038

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1307 AN: 3440

East Asian (EAS) AF: 0.361 AC: 1840 AN: 5100

South Asian (SAS) AF: 0.317 AC: 1527 AN: 4810

European-Finnish (FIN) AF: 0.491 AC: 5165 AN: 10516

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

European-Non Finnish (NFE) AF: 0.514 AC: 34408 AN: 66934

Other (OTH) AF: 0.515 AC: 1075 AN: 2088

Alfa AF: 0.538 Hom.: 2843

Bravo AF: 0.569

Asia WGS AF: 0.374 AC: 1297 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.9
DANN	Benign	0.44
PhyloP100		0.69
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: rs10938426; hg19: chr4-46118235;