rs2661319

Positions:

• chr1-163069987-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS4	NM_005613.6	c.44+459T>C		intron_variant		ENST00000367909.11
RGS4	NM_001102445.3	c.335+459T>C		intron_variant
RGS4	NM_001113381.1	c.44+459T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS4	ENST00000367909.11	c.44+459T>C		intron_variant		1	NM_005613.6	P1

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

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.472

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.562

Gnomad4 NFE AF: 0.516

Gnomad4 OTH AF: 0.435

Alfa AF: 0.495 Hom.: 19233

Bravo AF: 0.433

Asia WGS AF: 0.360 AC: 1254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.69

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: rs2661319; hg19: chr1-163039777;