rs12127281

Positions:

• chr1-163150963-C-T

Variant summary

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

The ENST00000313961.10(RGS5):​c.384+1587G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,092 control chromosomes in the GnomAD database, including 3,307 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 0.18 (3307 hom., cov: 32)
• Consequence: RGS5 ENST00000313961.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.136

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS5	NM_003617.4	c.384+1587G>A		intron_variant		ENST00000313961.10	NP_003608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS5	ENST00000313961.10	c.384+1587G>A		intron_variant		1	NM_003617.4	ENSP00000319308	P4

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27529 AN: 151974 Hom.: 3310 Cov.: 32

Gnomad AFR AF: 0.0476

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.0922

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.181 AC: 27528 AN: 152092 Hom.: 3307 Cov.: 32 AF XY: 0.175 AC XY: 12999 AN XY: 74352

Gnomad4 AFR AF: 0.0475

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.0926

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.197

Alfa AF: 0.261 Hom.: 7062

Bravo AF: 0.181

Asia WGS AF: 0.112 AC: 387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.8
DANN	Benign	0.67

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: rs12127281; hg19: chr1-163120753;