6-89197296-C-T

Variant names:

• chr6-89197296-C-T
• rs439912
• NM_002042.5:c.572+724G>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.572+724G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 151,586 control chromosomes in the GnomAD database, including 26,313 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 0.58 (26313 hom., cov: 32)
• Consequence: GABRR1 NM_002042.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.907 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR1	NM_002042.5	MANE Select	c.572+724G>A		intron	N/A	NP_002033.2	P24046-1
	GABRR1	NM_001256703.1		c.521+724G>A		intron	N/A	NP_001243632.1	P24046-2
	GABRR1	NM_001256704.1		c.311+724G>A		intron	N/A	NP_001243633.1	P24046-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR1	ENST00000454853.7	TSL:1 MANE Select	c.572+724G>A		intron	N/A	ENSP00000412673.2	P24046-1
	GABRR1	ENST00000435811.5	TSL:2	c.521+724G>A		intron	N/A	ENSP00000394687.1	P24046-2
	GABRR1	ENST00000369451.7	TSL:5	c.311+724G>A		intron	N/A	ENSP00000358463.3	P24046-3

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88438 AN: 151468 Hom.: 26296 Cov.: 32

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.584 AC: 88491 AN: 151586 Hom.: 26313 Cov.: 32 AF XY: 0.588 AC XY: 43556 AN XY: 74044

African (AFR) AF: 0.542 AC: 22407 AN: 41352

American (AMR) AF: 0.699 AC: 10674 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1957 AN: 3468

East Asian (EAS) AF: 0.929 AC: 4777 AN: 5140

South Asian (SAS) AF: 0.675 AC: 3249 AN: 4812

European-Finnish (FIN) AF: 0.578 AC: 6037 AN: 10452

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.552 AC: 37402 AN: 67808

Other (OTH) AF: 0.585 AC: 1233 AN: 2106

Alfa AF: 0.565 Hom.: 76579

Bravo AF: 0.593

Asia WGS AF: 0.775 AC: 2692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.6
DANN	Benign	0.77
PhyloP100		-0.11
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: rs439912; hg19: chr6-89907015; COSMIC: COSV65620453;