NM_002042.5:c.123-4599G>C

Variant names:

• chr6-89208084-C-G
• rs881293
• NM_002042.5:c.123-4599G>C

Variant summary

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

The NM_002042.5(GABRR1):​c.123-4599G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 152,162 control chromosomes in the GnomAD database, including 30,485 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 0.63 (30485 hom., cov: 33)
• Consequence: GABRR1 NM_002042.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.575
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002042.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR1	NM_002042.5	MANE Select	c.123-4599G>C		intron	N/A	NP_002033.2
	GABRR1	NM_001256703.1		c.123-6819G>C		intron	N/A	NP_001243632.1
	GABRR1	NM_001256704.1		c.-241-3390G>C		intron	N/A	NP_001243633.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR1	ENST00000454853.7	TSL:1 MANE Select	c.123-4599G>C		intron	N/A	ENSP00000412673.2
	GABRR1	ENST00000435811.5	TSL:2	c.123-6819G>C		intron	N/A	ENSP00000394687.1
	GABRR1	ENST00000369451.7	TSL:5	c.-238-3390G>C		intron	N/A	ENSP00000358463.3

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95365 AN: 152042 Hom.: 30464 Cov.: 33

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.758

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.663

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

GnomAD4 genome AF: 0.627 AC: 95447 AN: 152162 Hom.: 30485 Cov.: 33 AF XY: 0.616 AC XY: 45820 AN XY: 74404

African (AFR) AF: 0.595 AC: 24694 AN: 41498

American (AMR) AF: 0.625 AC: 9543 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2777 AN: 3470

East Asian (EAS) AF: 0.306 AC: 1583 AN: 5174

South Asian (SAS) AF: 0.686 AC: 3311 AN: 4826

European-Finnish (FIN) AF: 0.498 AC: 5274 AN: 10600

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 46028 AN: 68000

Other (OTH) AF: 0.662 AC: 1396 AN: 2110

Alfa AF: 0.500 Hom.: 1275

Bravo AF: 0.637

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.79
PhyloP100		-0.57
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: rs881293; hg19: chr6-89917803;