chr1-163168711-C-A

Variant names:

• chr1-163168711-C-A
• rs9628673
• NM_003617.4:c.45-343G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003617.4(RGS5):​c.45-343G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 151,774 control chromosomes in the GnomAD database, including 26,347 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 0.57 (26347 hom., cov: 30)
• Consequence: RGS5 NM_003617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.986
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS5	NM_003617.4	c.45-343G>T		intron_variant	Intron 1 of 4	ENST00000313961.10	NP_003608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS5	ENST00000313961.10	c.45-343G>T		intron_variant	Intron 1 of 4	1	NM_003617.4	ENSP00000319308.5

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86357 AN: 151656 Hom.: 26344 Cov.: 30

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.772

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.594

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

GnomAD4 genome AF: 0.569 AC: 86396 AN: 151774 Hom.: 26347 Cov.: 30 AF XY: 0.581 AC XY: 43066 AN XY: 74182

African (AFR) AF: 0.340 AC: 14063 AN: 41380

American (AMR) AF: 0.684 AC: 10433 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2292 AN: 3464

East Asian (EAS) AF: 0.622 AC: 3187 AN: 5124

South Asian (SAS) AF: 0.719 AC: 3441 AN: 4788

European-Finnish (FIN) AF: 0.772 AC: 8146 AN: 10546

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42754 AN: 67926

Other (OTH) AF: 0.594 AC: 1249 AN: 2102

Alfa AF: 0.592 Hom.: 39595

Bravo AF: 0.550

Asia WGS AF: 0.609 AC: 2119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.98
DANN	Benign	0.76
PhyloP100		-0.99
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9628673; hg19: chr1-163138501;