NM_002043.5:c.220+13073C>T

Variant names:

• chr6-89286686-G-A
• rs3798256
• NM_002043.5:c.220+13073C>T

Variant summary

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

The NM_002043.5(GABRR2):​c.220+13073C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 151,854 control chromosomes in the GnomAD database, including 24,522 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 0.57 (24522 hom., cov: 31)
• Consequence: GABRR2 NM_002043.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600
• Publications: 5 publications found

Genes affected

GABRR2 (HGNC:4091): (gamma-aminobutyric acid type A receptor subunit rho2) Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA receptors, which are ligand-gated chloride channels. The protein encoded by this gene is a member of the rho subunit family and is a component of the GABA type A receptor complex. This gene exists on chromosome 6q next to the gene encoding the rho 1 subunit of the GABA type A receptor, in a region thought to be associated with susceptibility for psychiatric disorders and epilepsy. Polymorphisms in this gene may also be associated with alcohol dependence, and general cognitive ability. [provided by RefSeq, Apr 2016]

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 = 0.678 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002043.5. 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
	GABRR2	NM_002043.5	MANE Select	c.220+13073C>T		intron	N/A	NP_002034.3	P28476-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR2	ENST00000402938.4	TSL:1 MANE Select	c.220+13073C>T		intron	N/A	ENSP00000386029.4	P28476-1
	GABRR2	ENST00000602808.1	TSL:3	n.354+13073C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.567 AC: 85970 AN: 151734 Hom.: 24513 Cov.: 31

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.574

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

GnomAD4 genome AF: 0.567 AC: 86030 AN: 151854 Hom.: 24522 Cov.: 31 AF XY: 0.570 AC XY: 42329 AN XY: 74232

African (AFR) AF: 0.565 AC: 23392 AN: 41390

American (AMR) AF: 0.550 AC: 8395 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1837 AN: 3470

East Asian (EAS) AF: 0.697 AC: 3601 AN: 5168

South Asian (SAS) AF: 0.658 AC: 3161 AN: 4806

European-Finnish (FIN) AF: 0.610 AC: 6423 AN: 10534

Middle Eastern (MID) AF: 0.531 AC: 155 AN: 292

European-Non Finnish (NFE) AF: 0.550 AC: 37378 AN: 67924

Other (OTH) AF: 0.577 AC: 1213 AN: 2102

Alfa AF: 0.544 Hom.: 36173

Bravo AF: 0.559

Asia WGS AF: 0.686 AC: 2385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.71
PhyloP100		-0.0060
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: rs3798256; hg19: chr6-89996405; COSMIC: COSV68766274;