rs2940675

Variant names:

• chr1-163215001-T-C
• rs2940675
• ENST00000367903.7:c.69+2525A>G

Variant summary

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

The ENST00000367903.7(RGS5):​c.69+2525A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 151,940 control chromosomes in the GnomAD database, including 13,056 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 0.40 (13056 hom., cov: 32)
• Consequence: RGS5 ENST00000367903.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.174
• Publications: 1 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 (AFR) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS5	NM_001414472.1	c.65+33529A>G		intron_variant	Intron 3 of 6		NP_001401401.1
RGS5	NM_001414473.1	c.65+33529A>G		intron_variant	Intron 5 of 8		NP_001401402.1
RGS5	NM_001414474.1	c.65+33529A>G		intron_variant	Intron 4 of 7		NP_001401403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS5	ENST00000367903.7	c.69+2525A>G		intron_variant	Intron 1 of 5	3		ENSP00000356879.3
RGS5	ENST00000618415.4	c.-280-46633A>G		intron_variant	Intron 2 of 5	4		ENSP00000480891.1
RGS5	ENST00000428971.2	n.447-46633A>G		intron_variant	Intron 4 of 5	5

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60561 AN: 151822 Hom.: 13043 Cov.: 32

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.399 AC: 60625 AN: 151940 Hom.: 13056 Cov.: 32 AF XY: 0.399 AC XY: 29600 AN XY: 74278

African (AFR) AF: 0.588 AC: 24368 AN: 41446

American (AMR) AF: 0.345 AC: 5264 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1208 AN: 3468

East Asian (EAS) AF: 0.296 AC: 1528 AN: 5160

South Asian (SAS) AF: 0.369 AC: 1775 AN: 4812

European-Finnish (FIN) AF: 0.339 AC: 3582 AN: 10558

Middle Eastern (MID) AF: 0.363 AC: 106 AN: 292

European-Non Finnish (NFE) AF: 0.320 AC: 21740 AN: 67934

Other (OTH) AF: 0.372 AC: 786 AN: 2112

Alfa AF: 0.438 Hom.: 5844

Bravo AF: 0.403

Asia WGS AF: 0.380 AC: 1319 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.85
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2940675; hg19: chr1-163184791;