1-192577922-G-T

Variant names:

• chr1-192577922-G-T
• rs10921202
• NM_002922.4:c.281-300G>T

Variant summary

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

The NM_002922.4(RGS1):​c.281-300G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0584 in 329,238 control chromosomes in the GnomAD database, including 682 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 0.053 (263 hom., cov: 32)
  • Exomes 𝑓: 0.063 (419 hom.)
• Consequence: RGS1 NM_002922.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.110
• Publications: 11 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0905 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002922.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS1	NM_002922.4	MANE Select	c.281-300G>T		intron	N/A	NP_002913.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS1	ENST00000367459.8	TSL:1 MANE Select	c.281-300G>T		intron	N/A	ENSP00000356429.3
	RGS1	ENST00000498352.1	TSL:2	n.1385G>T		non_coding_transcript_exon	Exon 3 of 4
	RGS1	ENST00000469578.2	TSL:2	c.281-300G>T		intron	N/A	ENSP00000464323.1

Frequencies

GnomAD3 genomes AF: 0.0531 AC: 8074 AN: 151984 Hom.: 261 Cov.: 32

Gnomad AFR AF: 0.0210

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0408

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0362

Gnomad SAS AF: 0.0968

Gnomad FIN AF: 0.0445

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0718

Gnomad OTH AF: 0.0561

GnomAD4 exome AF: 0.0629 AC: 11149 AN: 177136 Hom.: 419 Cov.: 3 AF XY: 0.0647 AC XY: 5963 AN XY: 92194

African (AFR) AF: 0.0226 AC: 127 AN: 5612

American (AMR) AF: 0.0373 AC: 260 AN: 6964

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 644 AN: 6158

East Asian (EAS) AF: 0.0225 AC: 278 AN: 12362

South Asian (SAS) AF: 0.0790 AC: 1088 AN: 13766

European-Finnish (FIN) AF: 0.0382 AC: 320 AN: 8384

Middle Eastern (MID) AF: 0.0592 AC: 51 AN: 862

European-Non Finnish (NFE) AF: 0.0689 AC: 7718 AN: 111974

Other (OTH) AF: 0.0600 AC: 663 AN: 11054

GnomAD4 genome AF: 0.0532 AC: 8088 AN: 152102 Hom.: 263 Cov.: 32 AF XY: 0.0509 AC XY: 3782 AN XY: 74354

African (AFR) AF: 0.0210 AC: 873 AN: 41518

American (AMR) AF: 0.0408 AC: 622 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 399 AN: 3464

East Asian (EAS) AF: 0.0363 AC: 188 AN: 5186

South Asian (SAS) AF: 0.0978 AC: 471 AN: 4818

European-Finnish (FIN) AF: 0.0445 AC: 472 AN: 10604

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0718 AC: 4879 AN: 67952

Other (OTH) AF: 0.0575 AC: 121 AN: 2106

Alfa AF: 0.0666 Hom.: 712

Bravo AF: 0.0500

Asia WGS AF: 0.0610 AC: 213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.1
DANN	Benign	0.49
PhyloP100		0.11
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: rs10921202; hg19: chr1-192547052;