NM_001105580.3:c.755-432C>T

Variant names:

• chr3-98002199-G-A
• rs1492053
• NM_001105580.3:c.755-432C>T

Variant summary

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

The NM_001105580.3(GABRR3):​c.755-432C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 151,940 control chromosomes in the GnomAD database, including 9,527 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 0.34 (9527 hom., cov: 32)
• Consequence: GABRR3 NM_001105580.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR3	NM_001105580.3	c.755-432C>T		intron_variant	Intron 7 of 9	ENST00000472788.6	NP_001099050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRR3	ENST00000472788.6	c.755-432C>T		intron_variant	Intron 7 of 9	5	NM_001105580.3	ENSP00000420790.1
GABRR3	ENST00000470589.1	n.502-432C>T		intron_variant	Intron 5 of 5	1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52105 AN: 151822 Hom.: 9518 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.343 AC: 52134 AN: 151940 Hom.: 9527 Cov.: 32 AF XY: 0.346 AC XY: 25696 AN XY: 74250

African (AFR) AF: 0.209 AC: 8665 AN: 41438

American (AMR) AF: 0.388 AC: 5913 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1630 AN: 3468

East Asian (EAS) AF: 0.505 AC: 2606 AN: 5164

South Asian (SAS) AF: 0.365 AC: 1757 AN: 4818

European-Finnish (FIN) AF: 0.400 AC: 4219 AN: 10548

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25896 AN: 67934

Other (OTH) AF: 0.371 AC: 782 AN: 2108

Alfa AF: 0.361 Hom.: 2081

Bravo AF: 0.338

Asia WGS AF: 0.415 AC: 1439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.91
DANN	Benign	0.53
PhyloP100		-0.33

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: rs1492053; hg19: chr3-97721043;