chr6-89203490-C-T

Position:

• chr6-89203490-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000454853.7(GABRR1):​c.123-5G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 1,600,630 control chromosomes in the GnomAD database, including 364,486 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.69 (35922 hom., cov: 32)
  • Exomes 𝑓: 0.67 (328564 hom.)
• Consequence: GABRR1 ENST00000454853.7 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.1825
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRR1	NM_002042.5	c.123-5G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000454853.7	NP_002033.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRR1	ENST00000454853.7	c.123-5G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002042.5	ENSP00000412673	P1
GABRR1	ENST00000369451.7	c.-139-5G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5		ENSP00000358463
GABRR1	ENST00000435811.5	c.123-2225G>A		intron_variant		2		ENSP00000394687
GABRR1	ENST00000457434.1	c.*84-5G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		5		ENSP00000410130

Frequencies

GnomAD3 genomes AF: 0.685 AC: 103950 AN: 151694 Hom.: 35885 Cov.: 32

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.919

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.673

GnomAD3 exomes AF: 0.703 AC: 176574 AN: 251096 Hom.: 62852 AF XY: 0.698 AC XY: 94697 AN XY: 135710

Gnomad AFR exome AF: 0.672

Gnomad AMR exome AF: 0.805

Gnomad ASJ exome AF: 0.648

Gnomad EAS exome AF: 0.916

Gnomad SAS exome AF: 0.695

Gnomad FIN exome AF: 0.700

Gnomad NFE exome AF: 0.651

Gnomad OTH exome AF: 0.693

GnomAD4 exome AF: 0.670 AC: 971383 AN: 1448818 Hom.: 328564 Cov.: 33 AF XY: 0.670 AC XY: 483764 AN XY: 721538

Gnomad4 AFR exome AF: 0.676

Gnomad4 AMR exome AF: 0.798

Gnomad4 ASJ exome AF: 0.649

Gnomad4 EAS exome AF: 0.906

Gnomad4 SAS exome AF: 0.694

Gnomad4 FIN exome AF: 0.696

Gnomad4 NFE exome AF: 0.654

Gnomad4 OTH exome AF: 0.685

GnomAD4 genome AF: 0.685 AC: 104033 AN: 151812 Hom.: 35922 Cov.: 32 AF XY: 0.689 AC XY: 51123 AN XY: 74194

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.740

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.918

Gnomad4 SAS AF: 0.705

Gnomad4 FIN AF: 0.704

Gnomad4 NFE AF: 0.657

Gnomad4 OTH AF: 0.675

Alfa AF: 0.658 Hom.: 34851

Bravo AF: 0.688

Asia WGS AF: 0.827 AC: 2875 AN: 3478

EpiCase AF: 0.661

EpiControl AF: 0.653

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	17
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.18
dbscSNV1_RF	Pathogenic	0.77
SpliceAI score (max)		0.71		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.71		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4590242; hg19: chr6-89913209; COSMIC: COSV65620511; COSMIC: COSV65620511;