1-192809029-A-T

Position:

• chr1-192809029-A-T

Variant summary

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

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: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

Genes affected

(HGNC:):

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.192809029A>T		intergenic_region
RGS2	NM_002923.4	c.-43A>T		upstream_gene_variant		ENST00000235382.7	NP_002914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS2	ENST00000235382.7	c.-43A>T		upstream_gene_variant		1	NM_002923.4	ENSP00000235382.5

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

GnomAD3 exomes AF: 0.121 AC: 30393 AN: 250212 Hom.: 2275 AF XY: 0.124 AC XY: 16799 AN XY: 135346

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 SAS exome AF: 0.0549

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

Gnomad4 AFR exome AF: 0.0320

Gnomad4 AMR exome AF: 0.0860

Gnomad4 ASJ exome AF: 0.189

Gnomad4 EAS exome AF: 0.0489

Gnomad4 SAS exome AF: 0.0556

Gnomad4 FIN exome AF: 0.0972

Gnomad4 NFE exome AF: 0.178

Gnomad4 OTH exome AF: 0.148

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

Gnomad4 AFR AF: 0.0381

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.0511

Gnomad4 SAS AF: 0.0610

Gnomad4 FIN AF: 0.0934

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.141

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.30
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

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