chr1-182654722-C-A

Variant names:

• chr1-182654722-C-A
• rs1287978
• NM_001102450.3:c.194-6419G>T

Variant summary

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

The NM_001102450.3(RGS8):​c.194-6419G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 152,092 control chromosomes in the GnomAD database, including 46,096 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 0.78 (46096 hom., cov: 32)
• Consequence: RGS8 NM_001102450.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.257
• Publications: 0 publications found

Genes affected

RGS8 (HGNC:16810): (regulator of G protein signaling 8) This gene is a member of the regulator of G protein signaling (RGS) family and encodes a protein with a single RGS domain. Regulator of G protein signaling (RGS) proteins are regulatory and structural components of G protein-coupled receptor complexes. They accelerate transit through the cycle of GTP binding and hydrolysis to GDP, thereby terminating signal transduction, but paradoxically, also accelerate receptor-stimulated activation. [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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS8	NM_001102450.3	c.194-6419G>T		intron_variant	Intron 6 of 7	ENST00000515211.2	NP_001095920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS8	ENST00000515211.2	c.194-6419G>T		intron_variant	Intron 6 of 7	4	NM_001102450.3	ENSP00000511884.1

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118202 AN: 151974 Hom.: 46058 Cov.: 32

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.742

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

GnomAD4 genome AF: 0.778 AC: 118297 AN: 152092 Hom.: 46096 Cov.: 32 AF XY: 0.776 AC XY: 57722 AN XY: 74346

African (AFR) AF: 0.807 AC: 33482 AN: 41492

American (AMR) AF: 0.743 AC: 11340 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2265 AN: 3470

East Asian (EAS) AF: 0.737 AC: 3820 AN: 5180

South Asian (SAS) AF: 0.769 AC: 3707 AN: 4820

European-Finnish (FIN) AF: 0.792 AC: 8362 AN: 10562

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.777 AC: 52854 AN: 67984

Other (OTH) AF: 0.743 AC: 1573 AN: 2116

Alfa AF: 0.765 Hom.: 11914

Bravo AF: 0.773

Asia WGS AF: 0.786 AC: 2732 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.38
DANN	Benign	0.39
PhyloP100		-0.26
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: rs1287978; hg19: chr1-182623857;