rs1186902

Variant names:

• chr6-89217243-T-C
• rs1186902
• NM_002042.5:c.80A>G

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 35 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002042.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR1	NM_002042.5	MANE Select	c.80A>G	p.His27Arg	missense	Exon 1 of 10	NP_002033.2	P24046-1
	GABRR1	NM_001256703.1		c.80A>G	p.His27Arg	missense	Exon 1 of 9	NP_001243632.1	P24046-2
	GABRR1	NM_001256704.1		c.-284A>G		5_prime_UTR	Exon 1 of 11	NP_001243633.1	P24046-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR1	ENST00000454853.7	TSL:1 MANE Select	c.80A>G	p.His27Arg	missense	Exon 1 of 10	ENSP00000412673.2	P24046-1
	GABRR1	ENST00000435811.5	TSL:2	c.80A>G	p.His27Arg	missense	Exon 1 of 9	ENSP00000394687.1	P24046-2
	GABRR1	ENST00000964580.1		c.80A>G	p.His27Arg	missense	Exon 1 of 6	ENSP00000634639.1

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

GnomAD2 exomes AF: 0.268 AC: 67282 AN: 251290 AF XY: 0.270

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 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

African (AFR) AF: 0.104 AC: 3497 AN: 33478

American (AMR) AF: 0.372 AC: 16619 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 8595 AN: 26132

East Asian (EAS) AF: 0.247 AC: 9789 AN: 39688

South Asian (SAS) AF: 0.287 AC: 24755 AN: 86240

European-Finnish (FIN) AF: 0.205 AC: 10938 AN: 53414

Middle Eastern (MID) AF: 0.248 AC: 1428 AN: 5768

European-Non Finnish (NFE) AF: 0.261 AC: 290535 AN: 1111752

Other (OTH) AF: 0.260 AC: 15711 AN: 60380

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

African (AFR) AF: 0.109 AC: 4521 AN: 41504

American (AMR) AF: 0.321 AC: 4905 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1187 AN: 3472

East Asian (EAS) AF: 0.277 AC: 1432 AN: 5170

South Asian (SAS) AF: 0.287 AC: 1378 AN: 4806

European-Finnish (FIN) AF: 0.214 AC: 2267 AN: 10576

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17757 AN: 67978

Other (OTH) AF: 0.240 AC: 508 AN: 2116

Alfa AF: 0.252 Hom.: 11981

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 v4.9

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
MetaRNN	Benign	0.0045	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.8
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.025
Sift	Uncertain	0.0070	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.021	B
Vest4		0.038
MPC		0.31
ClinPred		0.013	T
GERP RS		1.8
PromoterAI		0.021	Neutral
Varity_R		0.068
gMVP		0.17
Mutation Taster		=94/6	polymorphism (auto)

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

Other links and lift over

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