rs10218752

Variant names:

• chr1-163202078-T-C
• rs10218752
• NM_003617.4:c.44+714A>G

Variant summary

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

The NM_003617.4(RGS5):​c.44+714A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,020 control chromosomes in the GnomAD database, including 2,351 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 0.17 (2351 hom., cov: 32)
• Consequence: RGS5 NM_003617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.471
• Publications: 5 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 (NFE) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003617.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS5	NM_003617.4	MANE Select	c.44+714A>G		intron	N/A	NP_003608.1
	RGS5	NM_001414472.1		c.66-33710A>G		intron	N/A	NP_001401401.1
	RGS5	NM_001414473.1		c.66-33710A>G		intron	N/A	NP_001401402.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS5	ENST00000313961.10	TSL:1 MANE Select	c.44+714A>G		intron	N/A	ENSP00000319308.5
	RGS5	ENST00000527988.1	TSL:1	c.-108+714A>G		intron	N/A	ENSP00000432313.1
	RGS5	ENST00000367903.7	TSL:3	c.69+15448A>G		intron	N/A	ENSP00000356879.3

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26288 AN: 151902 Hom.: 2353 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.0883

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.173 AC: 26299 AN: 152020 Hom.: 2351 Cov.: 32 AF XY: 0.168 AC XY: 12494 AN XY: 74324

African (AFR) AF: 0.154 AC: 6388 AN: 41450

American (AMR) AF: 0.160 AC: 2444 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 688 AN: 3466

East Asian (EAS) AF: 0.0886 AC: 458 AN: 5172

South Asian (SAS) AF: 0.137 AC: 660 AN: 4812

European-Finnish (FIN) AF: 0.142 AC: 1507 AN: 10580

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13424 AN: 67964

Other (OTH) AF: 0.197 AC: 416 AN: 2114

Alfa AF: 0.193 Hom.: 4179

Bravo AF: 0.175

Asia WGS AF: 0.115 AC: 400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.75
PhyloP100		-0.47
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: rs10218752; hg19: chr1-163171868;