3-98020827-C-T

Variant names:

• chr3-98020827-C-T
• rs854580
• NM_001105580.3:c.239-3105G>A

Variant summary

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

The NM_001105580.3(GABRR3):​c.239-3105G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,200 control chromosomes in the GnomAD database, including 6,194 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 (6194 hom., cov: 30)
• Consequence: GABRR3 NM_001105580.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.728
• Publications: 1 publications found

Genes affected

GABRR3 (HGNC:17969): (gamma-aminobutyric acid type A receptor subunit rho3) The neurotransmitter gamma-aminobutyric acid (GABA) functions in the central nervous system to regulate synaptic transmission of neurons. This gene encodes one of three related subunits, which combine as homo- or hetero-pentamers to form GABA(C) receptors. In humans, some individuals contain a single-base polymorphism (dbSNP rs832032) that is predicted to inactivate the gene product. [provided by RefSeq, Jan 2012]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105580.3. 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
	GABRR3	NM_001105580.3	MANE Select	c.239-3105G>A		intron	N/A	NP_001099050.1	A8MPY1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR3	ENST00000472788.6	TSL:5 MANE Select	c.239-3105G>A		intron	N/A	ENSP00000420790.1	A8MPY1
	GABRR3	ENST00000470589.1	TSL:1	n.356-3105G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39447 AN: 151100 Hom.: 6197 Cov.: 30

Gnomad AFR AF: 0.0766

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.261 AC: 39439 AN: 151200 Hom.: 6194 Cov.: 30 AF XY: 0.265 AC XY: 19569 AN XY: 73800

African (AFR) AF: 0.0766 AC: 3163 AN: 41318

American (AMR) AF: 0.299 AC: 4528 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 975 AN: 3460

East Asian (EAS) AF: 0.435 AC: 2227 AN: 5116

South Asian (SAS) AF: 0.363 AC: 1735 AN: 4784

European-Finnish (FIN) AF: 0.370 AC: 3774 AN: 10200

Middle Eastern (MID) AF: 0.193 AC: 56 AN: 290

European-Non Finnish (NFE) AF: 0.327 AC: 22214 AN: 67856

Other (OTH) AF: 0.270 AC: 567 AN: 2098

Alfa AF: 0.257 Hom.: 825

Bravo AF: 0.244

Asia WGS AF: 0.364 AC: 1267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.59
PhyloP100		-0.73

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: rs854580; hg19: chr3-97739671;