rs422751

Variant names:

• chr6-89198154-G-A
• rs422751
• NM_002042.5:c.438C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-89198154-G-A
• chr6-89198154-G-C

Variant summary

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

The NM_002042.5(GABRR1):​c.438C>T​(p.Asp146Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 1,613,662 control chromosomes in the GnomAD database, including 550,706 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 (48079 hom., cov: 29)
  • Exomes 𝑓: 0.83 (502627 hom.)
• Consequence: GABRR1 NM_002042.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400

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=-0.46).
• BP7: Synonymous conserved (PhyloP=-0.004 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR1	NM_002042.5	c.438C>T	p.Asp146Asp	synonymous_variant	Exon 5 of 10	ENST00000454853.7	NP_002033.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRR1	ENST00000454853.7	c.438C>T	p.Asp146Asp	synonymous_variant	Exon 5 of 10	1	NM_002042.5	ENSP00000412673.2

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120021 AN: 151802 Hom.: 48046 Cov.: 29

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.834

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.957

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.911

Gnomad MID AF: 0.793

Gnomad NFE AF: 0.829

Gnomad OTH AF: 0.793

GnomAD3 exomes AF: 0.833 AC: 209412 AN: 251468 Hom.: 87930 AF XY: 0.829 AC XY: 112664 AN XY: 135908

Gnomad AFR exome AF: 0.652

Gnomad AMR exome AF: 0.885

Gnomad ASJ exome AF: 0.807

Gnomad EAS exome AF: 0.956

Gnomad SAS exome AF: 0.761

Gnomad FIN exome AF: 0.912

Gnomad NFE exome AF: 0.829

Gnomad OTH exome AF: 0.829

GnomAD4 exome AF: 0.828 AC: 1210130 AN: 1461742 Hom.: 502627 Cov.: 57 AF XY: 0.826 AC XY: 600332 AN XY: 727190

Gnomad4 AFR exome AF: 0.648

Gnomad4 AMR exome AF: 0.880

Gnomad4 ASJ exome AF: 0.805

Gnomad4 EAS exome AF: 0.964

Gnomad4 SAS exome AF: 0.760

Gnomad4 FIN exome AF: 0.910

Gnomad4 NFE exome AF: 0.829

Gnomad4 OTH exome AF: 0.819

GnomAD4 genome AF: 0.791 AC: 120110 AN: 151920 Hom.: 48079 Cov.: 29 AF XY: 0.796 AC XY: 59091 AN XY: 74268

Gnomad4 AFR AF: 0.659

Gnomad4 AMR AF: 0.834

Gnomad4 ASJ AF: 0.821

Gnomad4 EAS AF: 0.957

Gnomad4 SAS AF: 0.767

Gnomad4 FIN AF: 0.911

Gnomad4 NFE AF: 0.829

Gnomad4 OTH AF: 0.796

Alfa AF: 0.816 Hom.: 65145

Bravo AF: 0.782

Asia WGS AF: 0.837 AC: 2912 AN: 3478

EpiCase AF: 0.823

EpiControl AF: 0.823

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	2.4
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: rs422751; hg19: chr6-89907873; COSMIC: COSV65620945;