1-163076561-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005613.6(RGS4):c.*2001G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,428 control chromosomes in the GnomAD database, including 5,963 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 0.27 (5953 hom., cov: 32)
  • Exomes 𝑓: 0.22 (10 hom.)
• Consequence: RGS4 NM_005613.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.441

Genes affected

RGS4 (HGNC:10000): (regulator of G protein signaling 4) 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 4 belongs to this family. All RGS proteins share a conserved 120-amino acid sequence termed the RGS domain. Regulator of G protein signaling 4 protein is 37% identical to RGS1 and 97% identical to rat Rgs4. This protein negatively regulate signaling upstream or at the level of the heterotrimeric G protein and is localized in the cytoplasm. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS4	NM_005613.6	c.*2001G>T		3_prime_UTR_variant	5/5	ENST00000367909.11
RGS4	NM_001102445.3	c.*2001G>T		3_prime_UTR_variant	6/6
RGS4	NM_001113380.1	c.*2001G>T		3_prime_UTR_variant	5/5
RGS4	NM_001113381.1	c.*2170G>T		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS4	ENST00000367909.11	c.*2001G>T		3_prime_UTR_variant	5/5	1	NM_005613.6	P1
RGS4	ENST00000421743.6	c.*2001G>T		3_prime_UTR_variant	6/6	1
RGS4	ENST00000367908.8	c.*2170G>T		3_prime_UTR_variant	4/4	2
RGS4	ENST00000491263.1	n.3744G>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40695 AN: 151870 Hom.: 5959 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.262

GnomAD4 exome AF: 0.218 AC: 96 AN: 440 Hom.: 10 Cov.: 0 AF XY: 0.244 AC XY: 65 AN XY: 266

Gnomad4 FIN exome AF: 0.216

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.268 AC: 40704 AN: 151988 Hom.: 5953 Cov.: 32 AF XY: 0.266 AC XY: 19794 AN XY: 74282

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.260

Alfa AF: 0.289 Hom.: 9006

Bravo AF: 0.268

Asia WGS AF: 0.328 AC: 1139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	13
Dann	Benign	0.86

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: rs10759; hg19: chr1-163046351;