1-163167799-T-C

Variant names:

• chr1-163167799-T-C
• rs2456899
• NM_003617.4:c.155+459A>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.155+459A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,148 control chromosomes in the GnomAD database, including 1,496 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 0.13 (1496 hom., cov: 32)
• Consequence: RGS5 NM_003617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS5	NM_003617.4	c.155+459A>G		intron_variant	Intron 2 of 4	ENST00000313961.10	NP_003608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS5	ENST00000313961.10	c.155+459A>G		intron_variant	Intron 2 of 4	1	NM_003617.4	ENSP00000319308.5

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19707 AN: 152030 Hom.: 1499 Cov.: 32

Gnomad AFR AF: 0.0723

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.0844

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.129 AC: 19700 AN: 152148 Hom.: 1496 Cov.: 32 AF XY: 0.128 AC XY: 9523 AN XY: 74396

African (AFR) AF: 0.0721 AC: 2995 AN: 41542

American (AMR) AF: 0.0843 AC: 1289 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 664 AN: 3472

East Asian (EAS) AF: 0.123 AC: 635 AN: 5164

South Asian (SAS) AF: 0.149 AC: 720 AN: 4828

European-Finnish (FIN) AF: 0.152 AC: 1612 AN: 10572

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

European-Non Finnish (NFE) AF: 0.166 AC: 11310 AN: 67972

Other (OTH) AF: 0.125 AC: 263 AN: 2110

Alfa AF: 0.150 Hom.: 3174

Bravo AF: 0.122

Asia WGS AF: 0.126 AC: 436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.4
DANN	Benign	0.51
PhyloP100		-0.0050
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: rs2456899; hg19: chr1-163137589;