rs2344673

Positions:

• chr1-163148262-G-A
• chr1-163148262-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003617.4(RGS5):​c.385-759C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0929 in 151,920 control chromosomes in the GnomAD database, including 913 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 0.093 (913 hom., cov: 30)
• Consequence: RGS5 NM_003617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS5	NM_003617.4	c.385-759C>T		intron_variant		ENST00000313961.10	NP_003608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS5	ENST00000313961.10	c.385-759C>T		intron_variant		1	NM_003617.4	ENSP00000319308	P4

Frequencies

GnomAD3 genomes AF: 0.0929 AC: 14109 AN: 151802 Hom.: 912 Cov.: 30

Gnomad AFR AF: 0.0272

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0999

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0326

Gnomad FIN AF: 0.0791

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.0929 AC: 14107 AN: 151920 Hom.: 913 Cov.: 30 AF XY: 0.0878 AC XY: 6515 AN XY: 74242

Gnomad4 AFR AF: 0.0272

Gnomad4 AMR AF: 0.0997

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0330

Gnomad4 FIN AF: 0.0791

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.104

Alfa AF: 0.105 Hom.: 267

Bravo AF: 0.0949

Asia WGS AF: 0.0160 AC: 54 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs2344673; hg19: chr1-163118052;