chr6-89296206-T-C

Position:

• chr6-89296206-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002043.5(GABRR2):​c.220+3553A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 152,210 control chromosomes in the GnomAD database, including 40,511 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 0.73 (40511 hom., cov: 34)
• Consequence: GABRR2 NM_002043.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRR2	NM_002043.5	c.220+3553A>G		intron_variant		ENST00000402938.4	NP_002034.3
GABRR2	XM_047418599.1	c.295+3553A>G		intron_variant			XP_047274555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRR2	ENST00000402938.4	c.220+3553A>G		intron_variant		1	NM_002043.5	ENSP00000386029	P1
GABRR2	ENST00000602808.1	n.354+3553A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110571 AN: 152092 Hom.: 40482 Cov.: 34

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.781

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.746

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

GnomAD4 genome AF: 0.727 AC: 110655 AN: 152210 Hom.: 40511 Cov.: 34 AF XY: 0.732 AC XY: 54440 AN XY: 74414

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.781

Gnomad4 ASJ AF: 0.744

Gnomad4 EAS AF: 0.977

Gnomad4 SAS AF: 0.743

Gnomad4 FIN AF: 0.750

Gnomad4 NFE AF: 0.703

Gnomad4 OTH AF: 0.746

Alfa AF: 0.709 Hom.: 53049

Bravo AF: 0.729

Asia WGS AF: 0.841 AC: 2922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.8
DANN	Benign	0.67

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: rs2148174; hg19: chr6-90005925;