chr1-163184579-A-C

Variant names:

• chr1-163184579-A-C
• rs4132246
• NM_003617.4:c.45-16211T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003617.4(RGS5):​c.45-16211T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00773 in 152,196 control chromosomes in the GnomAD database, including 13 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 0.0077 (13 hom., cov: 32)
• Consequence: RGS5 NM_003617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193
• Publications: 1 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=-0.88).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00773 (1176/152196) while in subpopulation AFR AF = 0.0264 (1094/41516). AF 95% confidence interval is 0.0251. There are 13 homozygotes in GnomAd4. There are 570 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS5	NM_003617.4	c.45-16211T>G		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.45-16211T>G		intron_variant	Intron 1 of 4	1	NM_003617.4	ENSP00000319308.5

Frequencies

GnomAD3 genomes AF: 0.00774 AC: 1177 AN: 152078 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.0265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00526

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

GnomAD4 genome AF: 0.00773 AC: 1176 AN: 152196 Hom.: 13 Cov.: 32 AF XY: 0.00766 AC XY: 570 AN XY: 74424

African (AFR) AF: 0.0264 AC: 1094 AN: 41516

American (AMR) AF: 0.00347 AC: 53 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68008

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.00 Hom.: 123

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.9
DANN	Benign	0.73
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism

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: rs4132246; hg19: chr1-163154369;