6-89216483-C-T

Variant names:

• chr6-89216483-C-T
• rs17504587
• NM_002042.5:c.122+718G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002042.5(GABRR1):​c.122+718G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,116 control chromosomes in the GnomAD database, including 2,457 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 0.17 (2457 hom., cov: 32)
• Consequence: GABRR1 NM_002042.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.10
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR1	NM_002042.5	c.122+718G>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+718G>A		intron_variant	Intron 1 of 9	1	NM_002042.5	ENSP00000412673.2

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26223 AN: 151998 Hom.: 2455 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.172 AC: 26226 AN: 152116 Hom.: 2457 Cov.: 32 AF XY: 0.169 AC XY: 12537 AN XY: 74358

African (AFR) AF: 0.176 AC: 7315 AN: 41486

American (AMR) AF: 0.143 AC: 2182 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1044 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.200 AC: 961 AN: 4814

European-Finnish (FIN) AF: 0.123 AC: 1298 AN: 10574

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12805 AN: 67998

Other (OTH) AF: 0.192 AC: 405 AN: 2104

Alfa AF: 0.179 Hom.: 1928

Bravo AF: 0.173

Asia WGS AF: 0.0870 AC: 303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.041
DANN	Benign	0.70
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17504587; hg19: chr6-89926202;