6-89301791-G-T

Position:

• chr6-89301791-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRR2	NM_002043.5	c.114-1926C>A		intron_variant		ENST00000402938.4	NP_002034.3
GABRR2	XM_047418599.1	c.189-1926C>A		intron_variant			XP_047274555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRR2	ENST00000402938.4	c.114-1926C>A		intron_variant		1	NM_002043.5	ENSP00000386029	P1
TUBB3P1	ENST00000405796.1	n.9G>T		non_coding_transcript_exon_variant	1/1
GABRR2	ENST00000602808.1	n.248-1926C>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR exome AF: 0.450

Gnomad4 AMR exome AF: 0.744

Gnomad4 ASJ exome AF: 0.617

Gnomad4 EAS exome AF: 0.562

Gnomad4 SAS exome AF: 0.570

Gnomad4 FIN exome AF: 0.556

Gnomad4 NFE exome AF: 0.625

Gnomad4 OTH exome AF: 0.608

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

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.620

Gnomad4 SAS AF: 0.582

Gnomad4 FIN AF: 0.559

Gnomad4 NFE AF: 0.634

Gnomad4 OTH AF: 0.605

Alfa AF: 0.616 Hom.: 5911

Bravo AF: 0.591

Asia WGS AF: 0.587 AC: 2042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	3.0
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs2325202; hg19: chr6-90011510; COSMIC: COSV68266248;