NM_002042.5:c.122+4366G>A

Variant names:

• chr6-89212835-C-T
• rs1029057
• NM_002042.5:c.122+4366G>A

Variant summary

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

The NM_002042.5(GABRR1):​c.122+4366G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 151,856 control chromosomes in the GnomAD database, including 4,343 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 0.23 (4343 hom., cov: 31)
• Consequence: GABRR1 NM_002042.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

Genes affected

GABRR1 (HGNC:4090): (gamma-aminobutyric acid type A receptor subunit rho1) GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA receptors, which are ligand-gated chloride channels. GABRR1 is a member of the rho subunit family. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR1	NM_002042.5	c.122+4366G>A		intron_variant	Intron 1 of 9	ENST00000454853.7	NP_002033.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRR1	ENST00000454853.7	c.122+4366G>A		intron_variant	Intron 1 of 9	1	NM_002042.5	ENSP00000412673.2

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34973 AN: 151740 Hom.: 4332 Cov.: 31

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.231 AC: 35008 AN: 151856 Hom.: 4343 Cov.: 31 AF XY: 0.229 AC XY: 16975 AN XY: 74206

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.242

Alfa AF: 0.128 Hom.: 205

Bravo AF: 0.238

Asia WGS AF: 0.241 AC: 841 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.4
DANN	Benign	0.79

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: rs1029057; hg19: chr6-89922554;