1-163204636-T-C

Position:

• chr1-163204636-T-C

Variant summary

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

The NM_001414472.1(RGS5):​c.66-36268A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,110 control chromosomes in the GnomAD database, including 4,120 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 0.22 (4120 hom., cov: 32)
• Consequence: RGS5 NM_001414472.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210

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:):

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 (AFR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS5	NM_001414472.1	c.66-36268A>G		intron_variant			NP_001401401.1
RGS5	NM_001414473.1	c.66-36268A>G		intron_variant			NP_001401402.1
RGS5	NM_001414474.1	c.66-36268A>G		intron_variant			NP_001401403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS5	ENST00000367903.7	c.69+12890A>G		intron_variant		3		ENSP00000356879.3
RGS5	ENST00000618415.4	c.-280-36268A>G		intron_variant		4		ENSP00000480891.1
RGS5-AS1	ENST00000415437.1	n.259-2061T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33038 AN: 151994 Hom.: 4125 Cov.: 32

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0531

Gnomad SAS AF: 0.0832

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.217 AC: 33071 AN: 152110 Hom.: 4120 Cov.: 32 AF XY: 0.215 AC XY: 15988 AN XY: 74362

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.0532

Gnomad4 SAS AF: 0.0829

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.198

Alfa AF: 0.181 Hom.: 3527

Bravo AF: 0.220

Asia WGS AF: 0.118 AC: 410 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	6.6
DANN	Benign	0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2815271; hg19: chr1-163174426;