rs2344671

Positions:

• chr1-163071074-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005613.6(RGS4):​c.45-1321G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,090 control chromosomes in the GnomAD database, including 1,194 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 0.12 (1194 hom., cov: 32)
• Consequence: RGS4 NM_005613.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230

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]

RGS4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS4	NM_005613.6	c.45-1321G>A		intron_variant		ENST00000367909.11	NP_005604.1
RGS4	NM_001102445.3	c.336-1321G>A		intron_variant			NP_001095915.1
RGS4	NM_001113381.1	c.45-1321G>A		intron_variant			NP_001106852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS4	ENST00000367909.11	c.45-1321G>A		intron_variant		1	NM_005613.6	ENSP00000356885.6

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18502 AN: 151972 Hom.: 1191 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.0514

Gnomad SAS AF: 0.0842

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.122 AC: 18520 AN: 152090 Hom.: 1194 Cov.: 32 AF XY: 0.120 AC XY: 8909 AN XY: 74344

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.0511

Gnomad4 SAS AF: 0.0849

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.136

Alfa AF: 0.134 Hom.: 312

Bravo AF: 0.122

Asia WGS AF: 0.0930 AC: 322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.1
DANN	Benign	0.63

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: rs2344671; hg19: chr1-163040864;