1-163073464-G-A

Position:

• chr1-163073464-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_005613.6(RGS4):​c.220G>A​(p.Ala74Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000491 in 1,426,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: RGS4 NM_005613.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.70

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]

LOC124904446 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.32043833).
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS4	NM_005613.6	c.220G>A	p.Ala74Thr	missense_variant	4/5	ENST00000367909.11
LOC124904446	XR_007066703.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS4	ENST00000367909.11	c.220G>A	p.Ala74Thr	missense_variant	4/5	1	NM_005613.6	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000137 AC: 3 AN: 218786 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 117968

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000291

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000491 AC: 7 AN: 1426706 Hom.: 0 Cov.: 30 AF XY: 0.00000282 AC XY: 2 AN XY: 708360

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000636

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	1.0
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.84	T;T;T;.;T;T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.32	T;T;T;T;T;T
MetaSVM	Benign	-0.88	T
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.7	D;D;D;D;D;D
REVEL	Benign	0.13
Sift	Benign	0.066	T;T;T;T;T;T
Sift4G	Benign	0.086	T;T;T;T;T;T
Polyphen		0.57	.;P;.;.;.;.
Vest4		0.35
MVP		0.53
MPC		0.25
ClinPred		0.54	D
GERP RS		3.9
Varity_R		0.17
gMVP		0.12

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: rs146574298; hg19: chr1-163043254;