rs10494382

Positions:

• chr1-163137317-T-G

Variant summary

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

The ENST00000469495.5(RGS5):​n.167+15233A>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,050 control chromosomes in the GnomAD database, including 6,024 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 0.27 (6024 hom., cov: 32)
• Consequence: RGS5 ENST00000469495.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.220

Genes affected

RGS5 (HGNC:10001): (regulator of G protein signaling 5) This locus represents naturally occurring readthrough transcription between the neighboring LOC127814295 (uncharacterized LOC127814295) and RGS5 (regulator of G-protein signaling 5) genes on chromosome 1. Some variants of the readthrough transcript encode novel proteins with unique N-termini. [provided by RefSeq, Nov 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS5	ENST00000469495.5	n.167+15233A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41493 AN: 151930 Hom.: 6018 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.273 AC: 41517 AN: 152050 Hom.: 6024 Cov.: 32 AF XY: 0.280 AC XY: 20829 AN XY: 74314

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.300

Alfa AF: 0.288 Hom.: 12486

Bravo AF: 0.265

Asia WGS AF: 0.305 AC: 1060 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	11
DANN	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10494382; hg19: chr1-163107107;