rs12041294

chr1-163171701-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
RGS5	NM_003617.4	c.45-3333G>A		intron_variant		ENST00000313961.10
RGS5-AS1	NR_110699.1	n.258+8825C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS5	ENST00000313961.10	c.45-3333G>A		intron_variant		1	NM_003617.4	P4
RGS5-AS1	ENST00000415437.1	n.258+8825C>T		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.0579

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.411

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.258

Alfa AF: 0.277 Hom.: 4491

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

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: rs12041294; hg19: chr1-163141491;