1-163251007-T-C

Variant names:

• chr1-163251007-T-C
• rs10494390
• NM_001414472.1:c.-4-2409A>G

Variant summary

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

The NM_001414472.1(RGS5):​c.-4-2409A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,226 control chromosomes in the GnomAD database, including 1,959 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 (1959 hom., cov: 32)
• Consequence: RGS5 NM_001414472.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.349
• Publications: 14 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 Gene-Disease associations (from GenCC):

• essential hypertension, genetic

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000232995 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001414472.1. 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_001414472.1		c.-4-2409A>G		intron	N/A	NP_001401401.1
	RGS5	NM_001414473.1		c.-4-2409A>G		intron	N/A	NP_001401402.1
	RGS5	NM_001414474.1		c.-4-2409A>G		intron	N/A	NP_001401403.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS5	ENST00000618415.4	TSL:4	c.-281+55226A>G		intron	N/A	ENSP00000480891.1	O15539-2
	ENSG00000232995	ENST00000427213.5	TSL:3	n.229-2301A>G		intron	N/A
	RGS5	ENST00000428971.2	TSL:5	n.446+55226A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22273 AN: 152108 Hom.: 1958 Cov.: 32

Gnomad AFR AF: 0.0701

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.0292

Gnomad SAS AF: 0.0783

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.146 AC: 22284 AN: 152226 Hom.: 1959 Cov.: 32 AF XY: 0.146 AC XY: 10842 AN XY: 74416

African (AFR) AF: 0.0701 AC: 2913 AN: 41564

American (AMR) AF: 0.148 AC: 2269 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 672 AN: 3472

East Asian (EAS) AF: 0.0293 AC: 152 AN: 5190

South Asian (SAS) AF: 0.0786 AC: 379 AN: 4822

European-Finnish (FIN) AF: 0.233 AC: 2472 AN: 10592

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12984 AN: 67974

Other (OTH) AF: 0.143 AC: 301 AN: 2108

Alfa AF: 0.170 Hom.: 7176

Bravo AF: 0.137

Asia WGS AF: 0.0750 AC: 260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.53
PhyloP100		-0.35

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10494390; hg19: chr1-163220797;