rs12565879

Variant names:

• chr1-163179522-G-A
• rs12565879
• NM_003617.4:c.45-11154C>T

Variant summary

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

The NM_003617.4(RGS5):​c.45-11154C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 151,980 control chromosomes in the GnomAD database, including 3,449 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 0.20 (3449 hom., cov: 32)
• Consequence: RGS5 NM_003617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.862
• Publications: 1 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS5	NM_003617.4	c.45-11154C>T		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.45-11154C>T		intron_variant	Intron 1 of 4	1	NM_003617.4	ENSP00000319308.5

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30697 AN: 151864 Hom.: 3447 Cov.: 32

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.202 AC: 30714 AN: 151980 Hom.: 3449 Cov.: 32 AF XY: 0.203 AC XY: 15074 AN XY: 74290

African (AFR) AF: 0.302 AC: 12508 AN: 41454

American (AMR) AF: 0.147 AC: 2242 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 674 AN: 3466

East Asian (EAS) AF: 0.221 AC: 1142 AN: 5168

South Asian (SAS) AF: 0.290 AC: 1394 AN: 4812

European-Finnish (FIN) AF: 0.135 AC: 1421 AN: 10558

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10669 AN: 67942

Other (OTH) AF: 0.196 AC: 414 AN: 2108

Alfa AF: 0.191 Hom.: 388

Bravo AF: 0.203

Asia WGS AF: 0.257 AC: 894 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.66
PhyloP100		-0.86
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: rs12565879; hg19: chr1-163149312;