chr1-163184145-G-C

Position:

• chr1-163184145-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.45-15777C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,168 control chromosomes in the GnomAD database, including 1,500 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 0.12 (1500 hom., cov: 31)
• Consequence: RGS5 NM_003617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS5	NM_003617.4	c.45-15777C>G		intron_variant		ENST00000313961.10	NP_003608.1
RGS5-AS1	NR_110699.1	n.258+21269G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS5	ENST00000313961.10	c.45-15777C>G		intron_variant		1	NM_003617.4	ENSP00000319308	P4
RGS5-AS1	ENST00000415437.1	n.258+21269G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18337 AN: 152050 Hom.: 1502 Cov.: 31

Gnomad AFR AF: 0.0321

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.0853

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.00386

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.120 AC: 18331 AN: 152168 Hom.: 1500 Cov.: 31 AF XY: 0.117 AC XY: 8677 AN XY: 74390

Gnomad4 AFR AF: 0.0320

Gnomad4 AMR AF: 0.0851

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.00368

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.115

Alfa AF: 0.140 Hom.: 215

Bravo AF: 0.114

Asia WGS AF: 0.0850 AC: 300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.2
DANN	Benign	0.83

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: rs11586945; hg19: chr1-163153935;