chr1-163071076-G-T

Variant names:

• chr1-163071076-G-T
• rs12753561
• NM_005613.6:c.45-1319G>T

Variant summary

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

The NM_005613.6(RGS4):​c.45-1319G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,020 control chromosomes in the GnomAD database, including 4,567 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 0.24 (4567 hom., cov: 31)
• Consequence: RGS4 NM_005613.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.647
• Publications: 1 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 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.45-1319G>T		intron	N/A	NP_005604.1	P49798-1
	RGS4	NM_001102445.3		c.336-1319G>T		intron	N/A	NP_001095915.1	P49798-3
	RGS4	NM_001113381.1		c.45-1319G>T		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.45-1319G>T		intron	N/A	ENSP00000356885.6	P49798-1
	RGS4	ENST00000421743.6	TSL:1	c.336-1319G>T		intron	N/A	ENSP00000397181.2	P49798-3
	RGS4	ENST00000527809.5	TSL:4	c.-10-1319G>T		intron	N/A	ENSP00000433261.1	P49798-5

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36685 AN: 151902 Hom.: 4563 Cov.: 31

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.242 AC: 36722 AN: 152020 Hom.: 4567 Cov.: 31 AF XY: 0.245 AC XY: 18217 AN XY: 74320

African (AFR) AF: 0.264 AC: 10936 AN: 41480

American (AMR) AF: 0.227 AC: 3460 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 571 AN: 3464

East Asian (EAS) AF: 0.410 AC: 2113 AN: 5150

South Asian (SAS) AF: 0.399 AC: 1924 AN: 4820

European-Finnish (FIN) AF: 0.194 AC: 2055 AN: 10580

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14880 AN: 67954

Other (OTH) AF: 0.244 AC: 515 AN: 2112

Alfa AF: 0.218 Hom.: 732

Bravo AF: 0.241

Asia WGS AF: 0.390 AC: 1357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.42
DANN	Benign	0.55
PhyloP100		-0.65
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: rs12753561; hg19: chr1-163040866;