rs2841997

Variant names:

• chr1-163150449-G-A
• rs2841997
• NM_003617.4:c.384+2101C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-163150449-G-A
• chr1-163150449-G-T

Variant summary

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

The NM_003617.4(RGS5):​c.384+2101C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,054 control chromosomes in the GnomAD database, including 1,424 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 0.12 (1424 hom., cov: 32)
• Consequence: RGS5 NM_003617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS5	NM_003617.4	c.384+2101C>T		intron_variant	Intron 4 of 4	ENST00000313961.10	NP_003608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS5	ENST00000313961.10	c.384+2101C>T		intron_variant	Intron 4 of 4	1	NM_003617.4	ENSP00000319308.5

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18594 AN: 151938 Hom.: 1426 Cov.: 32

Gnomad AFR AF: 0.0529

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.0826

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.0823

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.122 AC: 18586 AN: 152054 Hom.: 1424 Cov.: 32 AF XY: 0.121 AC XY: 9008 AN XY: 74332

African (AFR) AF: 0.0528 AC: 2189 AN: 41496

American (AMR) AF: 0.0825 AC: 1259 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 663 AN: 3472

East Asian (EAS) AF: 0.0825 AC: 426 AN: 5166

South Asian (SAS) AF: 0.144 AC: 695 AN: 4814

European-Finnish (FIN) AF: 0.153 AC: 1615 AN: 10554

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11277 AN: 67972

Other (OTH) AF: 0.119 AC: 252 AN: 2112

Alfa AF: 0.131 Hom.: 246

Bravo AF: 0.113

Asia WGS AF: 0.0980 AC: 338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.3
DANN	Benign	0.41
PhyloP100		-0.23
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: rs2841997; hg19: chr1-163120239;