6-89203176-A-G

Position:

• chr6-89203176-A-G

Variant summary

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

The NM_002042.5(GABRR1):​c.173+259T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,042 control chromosomes in the GnomAD database, including 36,282 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 0.69 (36282 hom., cov: 31)
• Consequence: GABRR1 NM_002042.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.466

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• 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.173+259T>C		intron_variant		ENST00000454853.7	NP_002033.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRR1	ENST00000454853.7	c.173+259T>C		intron_variant		1	NM_002042.5	ENSP00000412673	P1
GABRR1	ENST00000369451.7	c.-89+259T>C		intron_variant		5		ENSP00000358463
GABRR1	ENST00000435811.5	c.123-1911T>C		intron_variant		2		ENSP00000394687
GABRR1	ENST00000457434.1	c.*134+259T>C		intron_variant, NMD_transcript_variant		5		ENSP00000410130

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104547 AN: 151924 Hom.: 36243 Cov.: 31

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.919

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.676

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

GnomAD4 genome AF: 0.688 AC: 104633 AN: 152042 Hom.: 36282 Cov.: 31 AF XY: 0.692 AC XY: 51406 AN XY: 74330

Gnomad4 AFR AF: 0.686

Gnomad4 AMR AF: 0.743

Gnomad4 ASJ AF: 0.645

Gnomad4 EAS AF: 0.919

Gnomad4 SAS AF: 0.706

Gnomad4 FIN AF: 0.706

Gnomad4 NFE AF: 0.657

Gnomad4 OTH AF: 0.677

Alfa AF: 0.686 Hom.: 5455

Bravo AF: 0.691

Asia WGS AF: 0.828 AC: 2881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.58
DANN	Benign	0.59

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: rs7741132; hg19: chr6-89912895; COSMIC: COSV65620497; COSMIC: COSV65620497;