rs914478

Variant names:

• chr6-89221200-T-C
• rs914478
• NM_001267582.2:c.-242+75A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001267582.2(GABRR1):​c.-242+75A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,098 control chromosomes in the GnomAD database, including 10,262 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 0.36 (10241 hom., cov: 31)
  • Exomes 𝑓: 0.39 (21 hom.)
• Consequence: GABRR1 NM_001267582.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472
• Publications: 5 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 (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR1	NM_001267582.2	c.-242+75A>G		intron_variant	Intron 2 of 11		NP_001254511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRR1	ENST00000369451.7	c.-239+75A>G		intron_variant	Intron 2 of 11	5		ENSP00000358463.3

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54230 AN: 151682 Hom.: 10234 Cov.: 31

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.0947

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.330

GnomAD4 exome AF: 0.389 AC: 116 AN: 298 Hom.: 21 AF XY: 0.400 AC XY: 72 AN XY: 180

African (AFR) AF: 0.333 AC: 2 AN: 6

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.418 AC: 46 AN: 110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.396 AC: 65 AN: 164

Other (OTH) AF: 0.200 AC: 2 AN: 10

GnomAD4 genome AF: 0.357 AC: 54264 AN: 151800 Hom.: 10241 Cov.: 31 AF XY: 0.352 AC XY: 26130 AN XY: 74178

African (AFR) AF: 0.450 AC: 18622 AN: 41348

American (AMR) AF: 0.233 AC: 3555 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 869 AN: 3466

East Asian (EAS) AF: 0.0945 AC: 489 AN: 5172

South Asian (SAS) AF: 0.271 AC: 1306 AN: 4818

European-Finnish (FIN) AF: 0.367 AC: 3868 AN: 10526

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.360 AC: 24432 AN: 67900

Other (OTH) AF: 0.328 AC: 693 AN: 2112

Alfa AF: 0.376 Hom.: 1406

Bravo AF: 0.350

Asia WGS AF: 0.262 AC: 911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.8
DANN	Benign	0.60
PhyloP100		-0.47
PromoterAI		0.036	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs914478; hg19: chr6-89930919;