rs4657251

Positions:

• chr1-163187074-T-C

Variant summary

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

The NM_003617.4(RGS5):​c.44+15718A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,038 control chromosomes in the GnomAD database, including 3,751 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 0.21 (3751 hom., cov: 32)
• Consequence: RGS5 NM_003617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS5	NM_003617.4	c.44+15718A>G		intron_variant		ENST00000313961.10	NP_003608.1
RGS5-AS1	NR_110699.1	n.259-19623T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS5	ENST00000313961.10	c.44+15718A>G		intron_variant		1	NM_003617.4	ENSP00000319308	P4
RGS5-AS1	ENST00000415437.1	n.259-19623T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31690 AN: 151920 Hom.: 3745 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.209 AC: 31716 AN: 152038 Hom.: 3751 Cov.: 32 AF XY: 0.210 AC XY: 15578 AN XY: 74314

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.197

Alfa AF: 0.190 Hom.: 377

Bravo AF: 0.210

Asia WGS AF: 0.261 AC: 909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.75

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: rs4657251; hg19: chr1-163156864;