6-89195453-A-G

Variant names:

• chr6-89195453-A-G
• rs9451177
• NM_002042.5:c.572+2567T>C

Variant summary

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

The NM_002042.5(GABRR1):​c.572+2567T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 148,990 control chromosomes in the GnomAD database, including 5,375 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 0.26 (5375 hom., cov: 30)
• Consequence: GABRR1 NM_002042.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR1	NM_002042.5	c.572+2567T>C		intron_variant	Intron 5 of 9	ENST00000454853.7	NP_002033.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRR1	ENST00000454853.7	c.572+2567T>C		intron_variant	Intron 5 of 9	1	NM_002042.5	ENSP00000412673.2
GABRR1	ENST00000435811.5	c.521+2567T>C		intron_variant	Intron 4 of 8	2		ENSP00000394687.1
GABRR1	ENST00000369451.7	c.311+2567T>C		intron_variant	Intron 7 of 11	5		ENSP00000358463.3
GABRR1	ENST00000457434.1	n.*533+2567T>C		intron_variant	Intron 6 of 10	5		ENSP00000410130.1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39181 AN: 148894 Hom.: 5371 Cov.: 30

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.0320

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.263 AC: 39205 AN: 148990 Hom.: 5375 Cov.: 30 AF XY: 0.259 AC XY: 18809 AN XY: 72588

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.0318

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.263

Alfa AF: 0.272 Hom.: 767

Bravo AF: 0.249

Asia WGS AF: 0.193 AC: 675 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.1
DANN	Benign	0.35

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: rs9451177; hg19: chr6-89905172;