rs7513108

Variant names:

• chr1-163193987-T-G
• rs7513108
• NM_003617.4:c.44+8805A>C

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+8805A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,102 control chromosomes in the GnomAD database, including 1,775 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 0.15 (1775 hom., cov: 32)
• Consequence: RGS5 NM_003617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS5	NM_003617.4	c.44+8805A>C		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.44+8805A>C		intron_variant	Intron 1 of 4	1	NM_003617.4	ENSP00000319308.5

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22908 AN: 151984 Hom.: 1773 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.151 AC: 22919 AN: 152102 Hom.: 1775 Cov.: 32 AF XY: 0.153 AC XY: 11355 AN XY: 74338

African (AFR) AF: 0.134 AC: 5582 AN: 41524

American (AMR) AF: 0.126 AC: 1923 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 664 AN: 3468

East Asian (EAS) AF: 0.226 AC: 1164 AN: 5160

South Asian (SAS) AF: 0.263 AC: 1266 AN: 4806

European-Finnish (FIN) AF: 0.143 AC: 1513 AN: 10584

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10257 AN: 67974

Other (OTH) AF: 0.155 AC: 327 AN: 2112

Alfa AF: 0.160 Hom.: 1112

Bravo AF: 0.146

Asia WGS AF: 0.242 AC: 841 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.74
PhyloP100		-0.019
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: rs7513108; hg19: chr1-163163777;