1-163110871-C-T

Variant names:

• chr1-163110871-C-T
• rs2841977
• ENST00000469495.5:n.*250G>A

Variant summary

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

The ENST00000469495.5(RGS5):​n.*250G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 151,162 control chromosomes in the GnomAD database, including 42,869 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 0.75 (42869 hom., cov: 29)
• Consequence: RGS5 ENST00000469495.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.84
• 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 Gene-Disease associations (from GenCC):

• essential hypertension, genetic

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS5	ENST00000469495.5	n.*250G>A		downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.745 AC: 112544 AN: 151048 Hom.: 42820 Cov.: 29

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.892

Gnomad SAS AF: 0.813

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.721

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.745 AC: 112655 AN: 151162 Hom.: 42869 Cov.: 29 AF XY: 0.750 AC XY: 55295 AN XY: 73772

African (AFR) AF: 0.900 AC: 37151 AN: 41288

American (AMR) AF: 0.722 AC: 10956 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 2428 AN: 3470

East Asian (EAS) AF: 0.891 AC: 4585 AN: 5144

South Asian (SAS) AF: 0.811 AC: 3880 AN: 4782

European-Finnish (FIN) AF: 0.707 AC: 7198 AN: 10180

Middle Eastern (MID) AF: 0.728 AC: 211 AN: 290

European-Non Finnish (NFE) AF: 0.649 AC: 44041 AN: 67826

Other (OTH) AF: 0.727 AC: 1523 AN: 2094

Alfa AF: 0.671 Hom.: 41776

Bravo AF: 0.750

Asia WGS AF: 0.841 AC: 2924 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.40
DANN	Benign	0.51
PhyloP100		-2.8

Splicing

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

Other links and lift over

dbSNP: rs2841977; hg19: chr1-163080661;