rs1323291

Positions:

• chr1-192579413-T-G

Variant summary

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

The NM_002922.4(RGS1):​c.*91T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,226,474 control chromosomes in the GnomAD database, including 9,264 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 0.16 (3224 hom., cov: 32)
  • Exomes 𝑓: 0.093 (6040 hom.)
• Consequence: RGS1 NM_002922.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.210

Genes affected

RGS1 (HGNC:9991): (regulator of G protein signaling 1) This gene encodes a member of the regulator of G-protein signalling family. This protein is located on the cytosolic side of the plasma membrane and contains a conserved, 120 amino acid motif called the RGS domain. The protein attenuates the signalling activity of G-proteins by binding to activated, GTP-bound G alpha subunits and acting as a GTPase activating protein (GAP), increasing the rate of conversion of the GTP to GDP. This hydrolysis allows the G alpha subunits to bind G beta/gamma subunit heterodimers, forming inactive G-protein heterotrimers, thereby terminating the signal. [provided by RefSeq, Jul 2008]

ENSG00000285280 (HGNC:49018): (RSG2 antisense RNA 1)

LOC105371664 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS1	NM_002922.4	c.*91T>G		3_prime_UTR_variant	5/5	ENST00000367459.8	NP_002913.3
LOC105371664	XR_002958418.2	n.288-12197A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS1	ENST00000367459.8	c.*91T>G		3_prime_UTR_variant	5/5	1	NM_002922.4	ENSP00000356429.3

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24143 AN: 151912 Hom.: 3219 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0885

Gnomad ASJ AF: 0.0478

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0759

Gnomad FIN AF: 0.0802

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0846

Gnomad OTH AF: 0.115

GnomAD4 exome AF: 0.0930 AC: 99875 AN: 1074446 Hom.: 6040 Cov.: 14 AF XY: 0.0907 AC XY: 49327 AN XY: 544068

Gnomad4 AFR exome AF: 0.396

Gnomad4 AMR exome AF: 0.0603

Gnomad4 ASJ exome AF: 0.0454

Gnomad4 EAS exome AF: 0.000139

Gnomad4 SAS exome AF: 0.0734

Gnomad4 FIN exome AF: 0.0777

Gnomad4 NFE exome AF: 0.0929

Gnomad4 OTH exome AF: 0.0952

GnomAD4 genome AF: 0.159 AC: 24172 AN: 152028 Hom.: 3224 Cov.: 32 AF XY: 0.155 AC XY: 11523 AN XY: 74326

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.0883

Gnomad4 ASJ AF: 0.0478

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0758

Gnomad4 FIN AF: 0.0802

Gnomad4 NFE AF: 0.0846

Gnomad4 OTH AF: 0.113

Alfa AF: 0.0922 Hom.: 958

Bravo AF: 0.170

Asia WGS AF: 0.0530 AC: 185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.9
DANN	Benign	0.81

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: rs1323291; hg19: chr1-192548543;