rs3777530

Positions:

• chr6-89199838-A-C
• chr6-89199838-A-G
• chr6-89199838-A-T

Variant summary

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

The NM_002042.5(GABRR1):​c.281-409T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 152,150 control chromosomes in the GnomAD database, including 48,495 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 0.79 (48495 hom., cov: 32)
• Consequence: GABRR1 NM_002042.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRR1	NM_002042.5	c.281-409T>G		intron_variant		ENST00000454853.7	NP_002033.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRR1	ENST00000454853.7	c.281-409T>G		intron_variant		1	NM_002042.5	ENSP00000412673.2
GABRR1	ENST00000435811.5	c.230-409T>G		intron_variant		2		ENSP00000394687.1
GABRR1	ENST00000369451.7	c.20-409T>G		intron_variant		5		ENSP00000358463.3
GABRR1	ENST00000457434.1	n.*242-409T>G		intron_variant		5		ENSP00000410130.1

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120669 AN: 152034 Hom.: 48462 Cov.: 32

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.958

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.912

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.800

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

GnomAD4 genome AF: 0.794 AC: 120758 AN: 152150 Hom.: 48495 Cov.: 32 AF XY: 0.799 AC XY: 59400 AN XY: 74380

Gnomad4 AFR AF: 0.665

Gnomad4 AMR AF: 0.837

Gnomad4 ASJ AF: 0.820

Gnomad4 EAS AF: 0.958

Gnomad4 SAS AF: 0.768

Gnomad4 FIN AF: 0.912

Gnomad4 NFE AF: 0.831

Gnomad4 OTH AF: 0.803

Alfa AF: 0.816 Hom.: 28941

Bravo AF: 0.786

Asia WGS AF: 0.838 AC: 2914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.6
DANN	Benign	0.64

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: rs3777530; hg19: chr6-89909557;