1-163197240-G-T

Variant summary

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

The NM_003617.4(RGS5):c.44+5552C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,846 control chromosomes in the GnomAD database, including 11,985 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 0.39 (11985 hom., cov: 31)
• Consequence: RGS5 NM_003617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.696

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 (AFR) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS5	NM_003617.4	c.44+5552C>A		intron_variant		ENST00000313961.10
RGS5-AS1	NR_110699.1	n.259-9457G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS5	ENST00000313961.10	c.44+5552C>A		intron_variant		1	NM_003617.4	P4
RGS5-AS1	ENST00000415437.1	n.259-9457G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58590 AN: 151728 Hom.: 11972 Cov.: 31

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.386 AC: 58650 AN: 151846 Hom.: 11985 Cov.: 31 AF XY: 0.385 AC XY: 28571 AN XY: 74226

Gnomad4 AFR AF: 0.535

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.367

Alfa AF: 0.217 Hom.: 452

Bravo AF: 0.387

Asia WGS AF: 0.361 AC: 1256 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	3.2
Dann	Benign	0.38

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: rs2999966; hg19: chr1-163167030;