4-46114415-A-G

Variant names:

• chr4-46114415-A-G
• rs12511372
• NM_173536.4:c.104+9395T>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+9395T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 150,754 control chromosomes in the GnomAD database, including 14,407 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 0.43 (14407 hom., cov: 31)
• Consequence: GABRG1 NM_173536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.486 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG1	NM_173536.4	MANE Select	c.104+9395T>C		intron	N/A	NP_775807.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG1	ENST00000295452.5	TSL:1 MANE Select	c.104+9395T>C		intron	N/A	ENSP00000295452.4

Frequencies

GnomAD3 genomes AF: 0.430 AC: 64765 AN: 150642 Hom.: 14398 Cov.: 31

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.430 AC: 64817 AN: 150754 Hom.: 14407 Cov.: 31 AF XY: 0.425 AC XY: 31277 AN XY: 73614

African (AFR) AF: 0.355 AC: 14652 AN: 41288

American (AMR) AF: 0.421 AC: 6339 AN: 15048

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1253 AN: 3442

East Asian (EAS) AF: 0.359 AC: 1833 AN: 5102

South Asian (SAS) AF: 0.310 AC: 1489 AN: 4808

European-Finnish (FIN) AF: 0.462 AC: 4871 AN: 10540

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.491 AC: 32984 AN: 67228

Other (OTH) AF: 0.422 AC: 884 AN: 2094

Alfa AF: 0.464 Hom.: 8743

Bravo AF: 0.429

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.9
DANN	Benign	0.73
PhyloP100		1.5
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: rs12511372; hg19: chr4-46116432;