6-89200045-C-T

Position:

• chr6-89200045-C-T

Variant summary

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

The NM_002042.5(GABRR1):​c.281-616G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 151,748 control chromosomes in the GnomAD database, including 13,550 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 0.41 (13550 hom., cov: 30)
• Consequence: GABRR1 NM_002042.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.638

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRR1	NM_002042.5	c.281-616G>A		intron_variant		ENST00000454853.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRR1	ENST00000454853.7	c.281-616G>A		intron_variant		1	NM_002042.5	P1
GABRR1	ENST00000369451.7	c.20-616G>A		intron_variant		5
GABRR1	ENST00000435811.5	c.230-616G>A		intron_variant		2
GABRR1	ENST00000457434.1	c.*242-616G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62820 AN: 151630 Hom.: 13525 Cov.: 30

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.0709

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.414 AC: 62887 AN: 151748 Hom.: 13550 Cov.: 30 AF XY: 0.410 AC XY: 30404 AN XY: 74162

Gnomad4 AFR AF: 0.465

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.0709

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.411

Alfa AF: 0.437 Hom.: 2983

Bravo AF: 0.407

Asia WGS AF: 0.223 AC: 779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.56
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: rs11967322; hg19: chr6-89909764;