rs2815272

Variant names:

• chr1-163203457-G-C
• rs2815272
• ENST00000367903.7:c.69+14069C>G

Variant summary

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

The ENST00000367903.7(RGS5):​c.69+14069C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0509 in 152,210 control chromosomes in the GnomAD database, including 627 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 0.051 (627 hom., cov: 32)
• Consequence: RGS5 ENST00000367903.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.485
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS5	NM_001414472.1	c.66-35089C>G		intron_variant	Intron 3 of 6		NP_001401401.1
RGS5	NM_001414473.1	c.66-35089C>G		intron_variant	Intron 5 of 8		NP_001401402.1
RGS5	NM_001414474.1	c.66-35089C>G		intron_variant	Intron 4 of 7		NP_001401403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS5	ENST00000367903.7	c.69+14069C>G		intron_variant	Intron 1 of 5	3		ENSP00000356879.3
RGS5	ENST00000618415.4	c.-280-35089C>G		intron_variant	Intron 2 of 5	4		ENSP00000480891.1
RGS5-AS1	ENST00000415437.1	n.259-3240G>C		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.0508 AC: 7729 AN: 152094 Hom.: 630 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0240

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.0154

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00160

Gnomad OTH AF: 0.0407

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

GnomAD4 genome AF: 0.0509 AC: 7743 AN: 152210 Hom.: 627 Cov.: 32 AF XY: 0.0487 AC XY: 3626 AN XY: 74426

African (AFR) AF: 0.169 AC: 7034 AN: 41508

American (AMR) AF: 0.0239 AC: 366 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3470

East Asian (EAS) AF: 0.0154 AC: 80 AN: 5180

South Asian (SAS) AF: 0.00394 AC: 19 AN: 4824

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10616

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00160 AC: 109 AN: 68012

Other (OTH) AF: 0.0450 AC: 95 AN: 2112

Alfa AF: 0.0376 Hom.: 48

Bravo AF: 0.0572

Asia WGS AF: 0.0360 AC: 125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.7
DANN	Benign	0.68
PhyloP100		0.48
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: rs2815272; hg19: chr1-163173247;