chr4-46038741-A-G

Position:

• chr4-46038741-A-G

Variant summary

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

The ENST00000295452.5(GABRG1):​c.*2247T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 150,978 control chromosomes in the GnomAD database, including 20,093 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 0.51 (20093 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: GABRG1 ENST00000295452.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.711

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRG1	NM_173536.4	c.*2247T>C		3_prime_UTR_variant	9/9	ENST00000295452.5	NP_775807.2
GABRG1	XM_017007990.2	c.*2247T>C		3_prime_UTR_variant	7/7		XP_016863479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRG1	ENST00000295452.5	c.*2247T>C		3_prime_UTR_variant	9/9	1	NM_173536.4	ENSP00000295452	P1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 76614 AN: 150860 Hom.: 20056 Cov.: 32

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.474

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.508 AC: 76721 AN: 150978 Hom.: 20093 Cov.: 32 AF XY: 0.507 AC XY: 37356 AN XY: 73694

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.421

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.552

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.472

Alfa AF: 0.457 Hom.: 14878

Bravo AF: 0.511

Asia WGS AF: 0.391 AC: 1349 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.64

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: rs1497568; hg19: chr4-46040758;