1-192809029-A-T

Variant names:

• chr1-192809029-A-T
• rs12130714
• ENST00000644058.2:n.202-42835T>A

Variant summary

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

The ENST00000644058.2(RGS2-AS1):​n.202-42835T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 1,439,086 control chromosomes in the GnomAD database, including 18,440 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 0.12 (1400 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17040 hom.)
• Consequence: RGS2-AS1 ENST00000644058.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 8 publications found

Genes affected

RGS2-AS1 (HGNC:49018): (RSG2 antisense RNA 1)

RGS2 (HGNC:9998): (regulator of G protein signaling 2) Regulator of G protein signaling (RGS) family members are regulatory molecules that act as GTPase activating proteins (GAPs) for G alpha subunits of heterotrimeric G proteins. RGS proteins are able to deactivate G protein subunits of the Gi alpha, Go alpha and Gq alpha subtypes. They drive G proteins into their inactive GDP-bound forms. Regulator of G protein signaling 2 belongs to this family. The protein acts as a mediator of myeloid differentiation and may play a role in leukemogenesis. [provided by RefSeq, Aug 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000644058.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS2	NM_002923.4	MANE Select	c.-43A>T		upstream_gene	N/A	NP_002914.1	P41220-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS2-AS1	ENST00000644058.2		n.202-42835T>A		intron	N/A
	RGS2-AS1	ENST00000644134.1		n.105-42835T>A		intron	N/A
	RGS2-AS1	ENST00000645822.1		n.200-16561T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18138 AN: 151978 Hom.: 1399 Cov.: 32

Gnomad AFR AF: 0.0382

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.0510

Gnomad SAS AF: 0.0599

Gnomad FIN AF: 0.0934

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.143

GnomAD2 exomes AF: 0.121 AC: 30393 AN: 250212 AF XY: 0.124

Gnomad AFR exome AF: 0.0337

Gnomad AMR exome AF: 0.0807

Gnomad ASJ exome AF: 0.185

Gnomad EAS exome AF: 0.0478

Gnomad FIN exome AF: 0.0904

Gnomad NFE exome AF: 0.176

Gnomad OTH exome AF: 0.145

GnomAD4 exome AF: 0.155 AC: 199370 AN: 1286990 Hom.: 17040 Cov.: 19 AF XY: 0.153 AC XY: 99147 AN XY: 649352

African (AFR) AF: 0.0320 AC: 962 AN: 30048

American (AMR) AF: 0.0860 AC: 3821 AN: 44428

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 4706 AN: 24960

East Asian (EAS) AF: 0.0489 AC: 1899 AN: 38830

South Asian (SAS) AF: 0.0556 AC: 4603 AN: 82756

European-Finnish (FIN) AF: 0.0972 AC: 5164 AN: 53130

Middle Eastern (MID) AF: 0.150 AC: 803 AN: 5336

European-Non Finnish (NFE) AF: 0.178 AC: 169354 AN: 953058

Other (OTH) AF: 0.148 AC: 8058 AN: 54444

GnomAD4 genome AF: 0.119 AC: 18135 AN: 152096 Hom.: 1400 Cov.: 32 AF XY: 0.114 AC XY: 8485 AN XY: 74374

African (AFR) AF: 0.0381 AC: 1581 AN: 41536

American (AMR) AF: 0.124 AC: 1896 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 691 AN: 3472

East Asian (EAS) AF: 0.0511 AC: 263 AN: 5142

South Asian (SAS) AF: 0.0610 AC: 294 AN: 4818

European-Finnish (FIN) AF: 0.0934 AC: 989 AN: 10588

Middle Eastern (MID) AF: 0.171 AC: 50 AN: 292

European-Non Finnish (NFE) AF: 0.175 AC: 11912 AN: 67940

Other (OTH) AF: 0.141 AC: 298 AN: 2110

Alfa AF: 0.0941 Hom.: 184

Bravo AF: 0.120

Asia WGS AF: 0.0660 AC: 231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.30
DANN	Benign	0.63
PhyloP100		-1.6
PromoterAI		-0.092	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12130714; hg19: chr1-192778159; COSMIC: COSV52458992;