1-163071076-G-T

Position:

• chr1-163071076-G-T

Variant summary

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

The ENST00000367909.11(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 ENST00000367909.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.647

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS4	NM_005613.6	c.45-1319G>T		intron_variant		ENST00000367909.11	NP_005604.1
RGS4	NM_001102445.3	c.336-1319G>T		intron_variant			NP_001095915.1
RGS4	NM_001113381.1	c.45-1319G>T		intron_variant			NP_001106852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS4	ENST00000367909.11	c.45-1319G>T		intron_variant		1	NM_005613.6	ENSP00000356885	P1

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

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.244

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.42
DANN	Benign	0.55

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: rs12753561; hg19: chr1-163040866;