1-163069987-T-C

Variant names:

• chr1-163069987-T-C
• rs2661319
• NM_005613.6:c.44+459T>C

Variant summary

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

The NM_005613.6(RGS4):​c.44+459T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 151,962 control chromosomes in the GnomAD database, including 15,518 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 0.44 (15518 hom., cov: 32)
• Consequence: RGS4 NM_005613.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470
• Publications: 37 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.511 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS4	NM_005613.6	MANE Select	c.44+459T>C		intron	N/A	NP_005604.1	P49798-1
	RGS4	NM_001102445.3		c.335+459T>C		intron	N/A	NP_001095915.1	P49798-3
	RGS4	NM_001113381.1		c.44+459T>C		intron	N/A	NP_001106852.1	P49798-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS4	ENST00000367909.11	TSL:1 MANE Select	c.44+459T>C		intron	N/A	ENSP00000356885.6	P49798-1
	RGS4	ENST00000421743.6	TSL:1	c.335+459T>C		intron	N/A	ENSP00000397181.2	P49798-3
	RGS4	ENST00000527809.5	TSL:4	c.-11+579T>C		intron	N/A	ENSP00000433261.1	P49798-5

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66478 AN: 151844 Hom.: 15526 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.437 AC: 66476 AN: 151962 Hom.: 15518 Cov.: 32 AF XY: 0.436 AC XY: 32407 AN XY: 74256

African (AFR) AF: 0.263 AC: 10894 AN: 41440

American (AMR) AF: 0.490 AC: 7482 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1639 AN: 3470

East Asian (EAS) AF: 0.465 AC: 2391 AN: 5144

South Asian (SAS) AF: 0.333 AC: 1602 AN: 4818

European-Finnish (FIN) AF: 0.562 AC: 5936 AN: 10568

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35027 AN: 67946

Other (OTH) AF: 0.435 AC: 918 AN: 2112

Alfa AF: 0.490 Hom.: 52706

Bravo AF: 0.433

Asia WGS AF: 0.360 AC: 1254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.69
PhyloP100		-0.47
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: rs2661319; hg19: chr1-163039777;