rs12041294

Variant names:

• chr1-163171701-C-T
• rs12041294
• NM_003617.4:c.45-3333G>A

Variant summary

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

The NM_003617.4(RGS5):​c.45-3333G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,000 control chromosomes in the GnomAD database, including 5,877 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 0.25 (5877 hom., cov: 33)
• Consequence: RGS5 NM_003617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.583
• Publications: 3 publications found

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]

RGS5-AS1 (HGNC:40504): (RGS5 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS5	NM_003617.4	c.45-3333G>A		intron_variant	Intron 1 of 4	ENST00000313961.10	NP_003608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS5	ENST00000313961.10	c.45-3333G>A		intron_variant	Intron 1 of 4	1	NM_003617.4	ENSP00000319308.5

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37279 AN: 151882 Hom.: 5869 Cov.: 33

Gnomad AFR AF: 0.0580

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.245 AC: 37292 AN: 152000 Hom.: 5877 Cov.: 33 AF XY: 0.256 AC XY: 19034 AN XY: 74280

African (AFR) AF: 0.0579 AC: 2402 AN: 41480

American (AMR) AF: 0.372 AC: 5676 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 789 AN: 3472

East Asian (EAS) AF: 0.425 AC: 2197 AN: 5164

South Asian (SAS) AF: 0.368 AC: 1776 AN: 4824

European-Finnish (FIN) AF: 0.411 AC: 4319 AN: 10512

Middle Eastern (MID) AF: 0.161 AC: 47 AN: 292

European-Non Finnish (NFE) AF: 0.285 AC: 19391 AN: 67964

Other (OTH) AF: 0.258 AC: 543 AN: 2108

Alfa AF: 0.271 Hom.: 5691

Bravo AF: 0.232

Asia WGS AF: 0.358 AC: 1246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.38
DANN	Benign	0.21
PhyloP100		-0.58
Mutation Taster		=100/0	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: rs12041294; hg19: chr1-163141491;