rs2940675

Positions:

• chr1-163215001-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
RGS5	NM_001254748.2	c.-280-46633A>G		intron_variant
RGS5	NM_001414472.1	c.65+33529A>G		intron_variant
RGS5	NM_001414473.1	c.65+33529A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS5	ENST00000367903.7	c.69+2525A>G		intron_variant		3
RGS5	ENST00000618415.4	c.-280-46633A>G		intron_variant		4
RGS5	ENST00000428971.2	n.447-46633A>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.588

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.372

Alfa AF: 0.377 Hom.: 1421

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2940675; hg19: chr1-163184791;