chr6-89217243-T-C

Position:

• chr6-89217243-T-C

Variant summary

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

The NM_002042.5(GABRR1):​c.80A>G​(p.His27Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,613,658 control chromosomes in the GnomAD database, including 55,646 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.23 (4286 hom., cov: 31)
  • Exomes 𝑓: 0.26 (51360 hom.)
• Consequence: GABRR1 NM_002042.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80

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]

GABRR1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0044744313).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRR1	NM_002042.5	c.80A>G	p.His27Arg	missense_variant	1/10	ENST00000454853.7	NP_002033.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRR1	ENST00000454853.7	c.80A>G	p.His27Arg	missense_variant	1/10	1	NM_002042.5	ENSP00000412673.2

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34206 AN: 151988 Hom.: 4274 Cov.: 31

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.236

GnomAD3 exomes AF: 0.268 AC: 67282 AN: 251290 Hom.: 9719 AF XY: 0.270 AC XY: 36602 AN XY: 135814

Gnomad AFR exome AF: 0.102

Gnomad AMR exome AF: 0.384

Gnomad ASJ exome AF: 0.336

Gnomad EAS exome AF: 0.266

Gnomad SAS exome AF: 0.285

Gnomad FIN exome AF: 0.208

Gnomad NFE exome AF: 0.257

Gnomad OTH exome AF: 0.281

GnomAD4 exome AF: 0.261 AC: 381867 AN: 1461552 Hom.: 51360 Cov.: 32 AF XY: 0.262 AC XY: 190726 AN XY: 727088

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.372

Gnomad4 ASJ exome AF: 0.329

Gnomad4 EAS exome AF: 0.247

Gnomad4 SAS exome AF: 0.287

Gnomad4 FIN exome AF: 0.205

Gnomad4 NFE exome AF: 0.261

Gnomad4 OTH exome AF: 0.260

GnomAD4 genome AF: 0.225 AC: 34245 AN: 152106 Hom.: 4286 Cov.: 31 AF XY: 0.224 AC XY: 16635 AN XY: 74348

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.240

Alfa AF: 0.255 Hom.: 8594

Bravo AF: 0.232

TwinsUK AF: 0.260 AC: 963

ALSPAC AF: 0.264 AC: 1016

ESP6500AA AF: 0.107 AC: 472

ESP6500EA AF: 0.269 AC: 2313

ExAC AF: 0.261 AC: 31689

Asia WGS AF: 0.240 AC: 835 AN: 3478

EpiCase AF: 0.267

EpiControl AF: 0.268

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Benign	0.85
DEOGEN2	Benign	0.028	T;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.58	T;T
MetaRNN	Benign	0.0045	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.26	N;N
REVEL	Benign	0.025
Sift	Uncertain	0.0070	D;T
Sift4G	Pathogenic	0.0	D;T
Polyphen		0.021	B;B
Vest4		0.038
MPC		0.31
ClinPred		0.013	T
GERP RS		1.8
Varity_R		0.068
gMVP		0.17

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: rs1186902; hg19: chr6-89926962; COSMIC: COSV65619035;