rs1287978

chr1-182654722-C-Achr1-182654722-C-Gchr1-182654722-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
RGS8	NM_001102450.3	c.194-6419G>T		intron_variant		ENST00000515211.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS8	ENST00000515211.2	c.194-6419G>T		intron_variant		4	NM_001102450.3	P1

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

Gnomad4 AFR AF: 0.807

Gnomad4 AMR AF: 0.743

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.737

Gnomad4 SAS AF: 0.769

Gnomad4 FIN AF: 0.792

Gnomad4 NFE AF: 0.777

Gnomad4 OTH AF: 0.743

Alfa AF: 0.748 Hom.: 4155

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

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: rs1287978; hg19: chr1-182623857;