rs2662774

Variant names:

• chr1-163191230-G-A
• rs2662774
• NM_003617.4:c.44+11562C>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.44+11562C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 151,996 control chromosomes in the GnomAD database, including 4,843 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 0.24 (4843 hom., cov: 32)
• Consequence: RGS5 NM_003617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.337 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS5	NM_003617.4	MANE Select	c.44+11562C>T		intron	N/A	NP_003608.1
	RGS5	NM_001414472.1		c.66-22862C>T		intron	N/A	NP_001401401.1
	RGS5	NM_001414473.1		c.66-22862C>T		intron	N/A	NP_001401402.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS5	ENST00000313961.10	TSL:1 MANE Select	c.44+11562C>T		intron	N/A	ENSP00000319308.5
	RGS5	ENST00000527988.1	TSL:1	c.-108+11562C>T		intron	N/A	ENSP00000432313.1
	RGS5	ENST00000367903.7	TSL:3	c.70-18638C>T		intron	N/A	ENSP00000356879.3

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36731 AN: 151876 Hom.: 4849 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.242 AC: 36760 AN: 151996 Hom.: 4843 Cov.: 32 AF XY: 0.240 AC XY: 17855 AN XY: 74296

African (AFR) AF: 0.342 AC: 14157 AN: 41414

American (AMR) AF: 0.210 AC: 3206 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 651 AN: 3468

East Asian (EAS) AF: 0.105 AC: 542 AN: 5174

South Asian (SAS) AF: 0.135 AC: 652 AN: 4816

European-Finnish (FIN) AF: 0.231 AC: 2437 AN: 10570

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14461 AN: 67976

Other (OTH) AF: 0.223 AC: 470 AN: 2110

Alfa AF: 0.233 Hom.: 1862

Bravo AF: 0.243

Asia WGS AF: 0.169 AC: 585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.0
DANN	Benign	0.72
PhyloP100		-1.4
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: rs2662774; hg19: chr1-163161020;