1-163076561-G-T

Variant names:

• chr1-163076561-G-T
• rs10759
• NM_005613.6:c.*2001G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005613.6. 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
	RGS4	NM_005613.6	MANE Select	c.*2001G>T		3_prime_UTR	Exon 5 of 5	NP_005604.1
	RGS4	NM_001102445.3		c.*2001G>T		3_prime_UTR	Exon 6 of 6	NP_001095915.1
	RGS4	NM_001113380.1		c.*2001G>T		3_prime_UTR	Exon 5 of 5	NP_001106851.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS4	ENST00000367909.11	TSL:1 MANE Select	c.*2001G>T		3_prime_UTR	Exon 5 of 5	ENSP00000356885.6
	RGS4	ENST00000421743.6	TSL:1	c.*2001G>T		3_prime_UTR	Exon 6 of 6	ENSP00000397181.2
	RGS4	ENST00000491263.1	TSL:2	n.3744G>T		non_coding_transcript_exon	Exon 3 of 3

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.216 AC: 93 AN: 430

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AF: 0.167 AC: 1 AN: 6

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

African (AFR) AF: 0.176 AC: 7294 AN: 41472

American (AMR) AF: 0.263 AC: 4012 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1026 AN: 3470

East Asian (EAS) AF: 0.411 AC: 2119 AN: 5150

South Asian (SAS) AF: 0.320 AC: 1539 AN: 4814

European-Finnish (FIN) AF: 0.266 AC: 2808 AN: 10556

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20848 AN: 67960

Other (OTH) AF: 0.260 AC: 548 AN: 2106

Alfa AF: 0.281 Hom.: 12157

Bravo AF: 0.268

Asia WGS AF: 0.328 AC: 1139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	13
DANN	Benign	0.86
PhyloP100		0.44
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: rs10759; hg19: chr1-163046351;