rs2036702

Positions:

• chr1-163212144-C-A
• chr1-163212144-C-T

Variant summary

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

The NM_001414472.1(RGS5):​c.65+36386G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,132 control chromosomes in the GnomAD database, including 1,499 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 0.14 (1499 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: RGS5 NM_001414472.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.355

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=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS5	NM_001414472.1	c.65+36386G>T		intron_variant			NP_001401401.1
RGS5	NM_001414473.1	c.65+36386G>T		intron_variant			NP_001401402.1
RGS5	NM_001414474.1	c.65+36386G>T		intron_variant			NP_001401403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS5	ENST00000367903.7	c.69+5382G>T		intron_variant		3		ENSP00000356879.3
RGS5	ENST00000618415.4	c.-280-43776G>T		intron_variant		4		ENSP00000480891.1
RGS5-AS1	ENST00000415437.1	n.1754C>A		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20869 AN: 152008 Hom.: 1500 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.0390

Gnomad SAS AF: 0.0734

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.133

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.137 AC: 20880 AN: 152126 Hom.: 1499 Cov.: 32 AF XY: 0.137 AC XY: 10156 AN XY: 74376

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.0387

Gnomad4 SAS AF: 0.0738

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.132

Alfa AF: 0.139 Hom.: 2025

Bravo AF: 0.136

Asia WGS AF: 0.0790 AC: 273 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.6
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2036702; hg19: chr1-163181934;