rs3777514

Variant names:

• chr6-89310862-G-T
• rs3777514
• NM_002043.5:c.113+4191C>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.113+4191C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,020 control chromosomes in the GnomAD database, including 5,433 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 0.26 (5433 hom., cov: 32)
• Consequence: GABRR2 NM_002043.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR2	NM_002043.5	c.113+4191C>A		intron_variant	Intron 1 of 8	ENST00000402938.4	NP_002034.3
GABRR2	XM_047418599.1	c.188+4191C>A		intron_variant	Intron 1 of 9		XP_047274555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRR2	ENST00000402938.4	c.113+4191C>A		intron_variant	Intron 1 of 8	1	NM_002043.5	ENSP00000386029.4
GABRR2	ENST00000602808.1	n.247+4191C>A		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39190 AN: 151902 Hom.: 5429 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.343

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.258 AC: 39231 AN: 152020 Hom.: 5433 Cov.: 32 AF XY: 0.259 AC XY: 19215 AN XY: 74320

African (AFR) AF: 0.369 AC: 15302 AN: 41416

American (AMR) AF: 0.239 AC: 3650 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1069 AN: 3472

East Asian (EAS) AF: 0.194 AC: 1000 AN: 5162

South Asian (SAS) AF: 0.305 AC: 1470 AN: 4822

European-Finnish (FIN) AF: 0.172 AC: 1822 AN: 10570

Middle Eastern (MID) AF: 0.348 AC: 101 AN: 290

European-Non Finnish (NFE) AF: 0.206 AC: 14035 AN: 67980

Other (OTH) AF: 0.257 AC: 542 AN: 2112

Alfa AF: 0.228 Hom.: 3126

Bravo AF: 0.266

Asia WGS AF: 0.265 AC: 923 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.0
DANN	Benign	0.76
PhyloP100		0.089
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: rs3777514; hg19: chr6-90020581;