1-163073298-A-G

Variant names:

• chr1-163073298-A-G
• rs10799897
• NM_005613.6:c.212-158A>G

Variant summary

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

The NM_005613.6(RGS4):​c.212-158A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 151,908 control chromosomes in the GnomAD database, including 18,864 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 0.49 (18864 hom., cov: 31)
• Consequence: RGS4 NM_005613.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.309
• Publications: 7 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]

LOC124904446 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.622 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.212-158A>G		intron	N/A	NP_005604.1
	RGS4	NM_001102445.3		c.503-158A>G		intron	N/A	NP_001095915.1
	RGS4	NM_001113380.1		c.158-158A>G		intron	N/A	NP_001106851.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS4	ENST00000367909.11	TSL:1 MANE Select	c.212-158A>G		intron	N/A	ENSP00000356885.6
	RGS4	ENST00000421743.6	TSL:1	c.503-158A>G		intron	N/A	ENSP00000397181.2
	RGS4	ENST00000367906.7	TSL:1	c.158-158A>G		intron	N/A	ENSP00000356882.3

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75019 AN: 151790 Hom.: 18835 Cov.: 31

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.505

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.494 AC: 75112 AN: 151908 Hom.: 18864 Cov.: 31 AF XY: 0.499 AC XY: 37056 AN XY: 74220

African (AFR) AF: 0.571 AC: 23660 AN: 41412

American (AMR) AF: 0.477 AC: 7266 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1747 AN: 3472

East Asian (EAS) AF: 0.411 AC: 2110 AN: 5138

South Asian (SAS) AF: 0.641 AC: 3090 AN: 4818

European-Finnish (FIN) AF: 0.470 AC: 4971 AN: 10578

Middle Eastern (MID) AF: 0.534 AC: 156 AN: 292

European-Non Finnish (NFE) AF: 0.451 AC: 30627 AN: 67934

Other (OTH) AF: 0.508 AC: 1074 AN: 2114

Alfa AF: 0.464 Hom.: 7598

Bravo AF: 0.488

Asia WGS AF: 0.573 AC: 1991 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	13
DANN	Benign	0.85
PhyloP100		0.31
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: rs10799897; hg19: chr1-163043088;