6-89301791-G-T

Variant names:

• chr6-89301791-G-T
• rs2325202
• NM_002043.5:c.114-1926C>A

Variant summary

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

The NM_002043.5(GABRR2):​c.114-1926C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 797,292 control chromosomes in the GnomAD database, including 149,355 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 (25827 hom., cov: 23)
  • Exomes 𝑓: 0.61 (123528 hom.)
• Consequence: GABRR2 NM_002043.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330
• Publications: 4 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]

TUBB3P1 (HGNC:42339): (tubulin beta 3 class III pseudogene 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.68 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.114-1926C>A		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.114-1926C>A		intron	N/A	ENSP00000386029.4	P28476-1
	TUBB3P1	ENST00000405796.1	TSL:6	n.9G>T		non_coding_transcript_exon	Exon 1 of 1
	GABRR2	ENST00000602808.1	TSL:3	n.248-1926C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.583 AC: 86303 AN: 148004 Hom.: 25814 Cov.: 23

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.613

GnomAD4 exome AF: 0.613 AC: 397803 AN: 649170 Hom.: 123528 Cov.: 8 AF XY: 0.611 AC XY: 213421 AN XY: 349390

African (AFR) AF: 0.450 AC: 8010 AN: 17788

American (AMR) AF: 0.744 AC: 29079 AN: 39072

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 12373 AN: 20038

East Asian (EAS) AF: 0.562 AC: 19108 AN: 33976

South Asian (SAS) AF: 0.570 AC: 38499 AN: 67572

European-Finnish (FIN) AF: 0.556 AC: 23669 AN: 42600

Middle Eastern (MID) AF: 0.620 AC: 2540 AN: 4098

European-Non Finnish (NFE) AF: 0.625 AC: 244609 AN: 391244

Other (OTH) AF: 0.608 AC: 19916 AN: 32782

GnomAD4 genome AF: 0.583 AC: 86360 AN: 148122 Hom.: 25827 Cov.: 23 AF XY: 0.582 AC XY: 41853 AN XY: 71968

African (AFR) AF: 0.456 AC: 18158 AN: 39862

American (AMR) AF: 0.691 AC: 10185 AN: 14734

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2101 AN: 3456

East Asian (EAS) AF: 0.620 AC: 3110 AN: 5016

South Asian (SAS) AF: 0.582 AC: 2621 AN: 4506

European-Finnish (FIN) AF: 0.559 AC: 5639 AN: 10092

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.634 AC: 42608 AN: 67256

Other (OTH) AF: 0.605 AC: 1219 AN: 2016

Alfa AF: 0.613 Hom.: 10746

Bravo AF: 0.591

Asia WGS AF: 0.587 AC: 2042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	3.0
DANN	Benign	0.82
PhyloP100		0.033
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: rs2325202; hg19: chr6-90011510; COSMIC: COSV68266248;