rs12035879

chr1-163172765-G-A

Variant summary

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

The NM_003617.4(RGS5):c.45-4397C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 152,064 control chromosomes in the GnomAD database, including 9,506 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 0.34 (9506 hom., cov: 32)
• Consequence: RGS5 NM_003617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.161

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-AS1 (HGNC:40504): (RGS5 antisense RNA 1)

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 (AMR) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS5	NM_003617.4	c.45-4397C>T		intron_variant		ENST00000313961.10
RGS5-AS1	NR_110699.1	n.258+9889G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS5	ENST00000313961.10	c.45-4397C>T		intron_variant		1	NM_003617.4	P4
RGS5-AS1	ENST00000415437.1	n.258+9889G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50948 AN: 151944 Hom.: 9499 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.335 AC: 50973 AN: 152064 Hom.: 9506 Cov.: 32 AF XY: 0.341 AC XY: 25374 AN XY: 74342

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.431

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.349

Alfa AF: 0.378 Hom.: 10819

Bravo AF: 0.328

Asia WGS AF: 0.376 AC: 1305 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.9
Dann	Benign	0.39

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: rs12035879; hg19: chr1-163142555; COSMIC: COSV58351714;