1-163068978-G-C

Variant names:

• chr1-163068978-G-C
• rs151032270
• ENST00000421743.6:c.44G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001102445.3(RGS4):​c.44G>C​(p.Gly15Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G15E) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RGS4 NM_001102445.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.703
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0665431).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001102445.3. 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_001102445.3		c.44G>C	p.Gly15Ala	missense	Exon 1 of 6	NP_001095915.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS4	ENST00000421743.6	TSL:1	c.44G>C	p.Gly15Ala	missense	Exon 1 of 6	ENSP00000397181.2
	RGS4	ENST00000527393.5	TSL:4	n.44G>C		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454874 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 722940

African (AFR) AF: 0.00 AC: 0 AN: 33374

American (AMR) AF: 0.0000227 AC: 1 AN: 44032

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25926

East Asian (EAS) AF: 0.00 AC: 0 AN: 39404

South Asian (SAS) AF: 0.00 AC: 0 AN: 84532

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53046

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108712

Other (OTH) AF: 0.00 AC: 0 AN: 60102

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.88
DANN	Benign	0.87
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.70
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.031
Sift	Pathogenic	0.0	D
Vest4		0.098
MutPred		0.32		Loss of loop (P = 0.0022)
MVP		0.21
MPC		0.24
ClinPred		0.12	T
GERP RS		-2.9
PromoterAI		0.19	Neutral
gMVP		0.084
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs151032270; hg19: chr1-163038768;