6-89179025-C-T

Position:

• chr6-89179025-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_002042.5(GABRR1):​c.1185G>A​(p.Ala395Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 1,613,682 control chromosomes in the GnomAD database, including 111,594 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 0.40 (12702 hom., cov: 31)
  • Exomes 𝑓: 0.36 (98892 hom.)
• Consequence: GABRR1 NM_002042.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31

Genes affected

GABRR1 (HGNC:4090): (gamma-aminobutyric acid type A receptor subunit rho1) GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA receptors, which are ligand-gated chloride channels. GABRR1 is a member of the rho subunit family. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP7: Synonymous conserved (PhyloP=2.31 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRR1	NM_002042.5	c.1185G>A	p.Ala395Ala	synonymous_variant	10/10	ENST00000454853.7	NP_002033.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRR1	ENST00000454853.7	c.1185G>A	p.Ala395Ala	synonymous_variant	10/10	1	NM_002042.5	ENSP00000412673.2

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60822 AN: 151826 Hom.: 12697 Cov.: 31

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.375

GnomAD3 exomes AF: 0.392 AC: 98348 AN: 251054 Hom.: 20378 AF XY: 0.384 AC XY: 52111 AN XY: 135722

Gnomad AFR exome AF: 0.466

Gnomad AMR exome AF: 0.396

Gnomad ASJ exome AF: 0.281

Gnomad EAS exome AF: 0.648

Gnomad SAS exome AF: 0.365

Gnomad FIN exome AF: 0.496

Gnomad NFE exome AF: 0.337

Gnomad OTH exome AF: 0.351

GnomAD4 exome AF: 0.362 AC: 529478 AN: 1461738 Hom.: 98892 Cov.: 48 AF XY: 0.360 AC XY: 262114 AN XY: 727178

Gnomad4 AFR exome AF: 0.467

Gnomad4 AMR exome AF: 0.395

Gnomad4 ASJ exome AF: 0.281

Gnomad4 EAS exome AF: 0.627

Gnomad4 SAS exome AF: 0.365

Gnomad4 FIN exome AF: 0.492

Gnomad4 NFE exome AF: 0.344

Gnomad4 OTH exome AF: 0.369

GnomAD4 genome AF: 0.401 AC: 60879 AN: 151944 Hom.: 12702 Cov.: 31 AF XY: 0.410 AC XY: 30482 AN XY: 74260

Gnomad4 AFR AF: 0.465

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.639

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.376

Alfa AF: 0.350 Hom.: 19840

Bravo AF: 0.395

Asia WGS AF: 0.477 AC: 1659 AN: 3478

EpiCase AF: 0.335

EpiControl AF: 0.332

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	7.9
DANN	Benign	0.44

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: rs1796743; hg19: chr6-89888744; COSMIC: COSV65619479;