chr1-163184579-A-G

Variant names:

• chr1-163184579-A-G
• rs4132246
• NM_003617.4:c.45-16211T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003617.4(RGS5):​c.45-16211T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,142 control chromosomes in the GnomAD database, including 3,291 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 (3291 hom., cov: 32)
• Consequence: RGS5 NM_003617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS5	NM_003617.4	c.45-16211T>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.45-16211T>C		intron_variant	Intron 1 of 4	1	NM_003617.4	ENSP00000319308.5

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30233 AN: 152024 Hom.: 3287 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.199 AC: 30254 AN: 152142 Hom.: 3291 Cov.: 32 AF XY: 0.200 AC XY: 14875 AN XY: 74400

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.190

Alfa AF: 0.0737 Hom.: 90

Bravo AF: 0.201

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.2
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs4132246; hg19: chr1-163154369;