4-46085255-T-G

Variant names:

• chr4-46085255-T-G
• rs1826923
• NM_173536.4:c.254-1202A>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173536.4(GABRG1):​c.254-1202A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 151,024 control chromosomes in the GnomAD database, including 26,418 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 0.58 (26418 hom., cov: 31)
• Consequence: GABRG1 NM_173536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG1	NM_173536.4	c.254-1202A>C		intron_variant	Intron 2 of 8	ENST00000295452.5	NP_775807.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG1	ENST00000295452.5	c.254-1202A>C		intron_variant	Intron 2 of 8	1	NM_173536.4	ENSP00000295452.4

Frequencies

GnomAD3 genomes AF: 0.583 AC: 87988 AN: 150904 Hom.: 26374 Cov.: 31

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.583 AC: 88102 AN: 151024 Hom.: 26418 Cov.: 31 AF XY: 0.580 AC XY: 42749 AN XY: 73752

Gnomad4 AFR AF: 0.692

Gnomad4 AMR AF: 0.547

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.641

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.544

Alfa AF: 0.469 Hom.: 1404

Bravo AF: 0.584

Asia WGS AF: 0.395 AC: 1372 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.6
DANN	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs1826923; hg19: chr4-46087272;