1-182651763-G-A

Position:

• chr1-182651763-G-A

Variant summary

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

The NM_001102450.3(RGS8):​c.194-3460C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 152,086 control chromosomes in the GnomAD database, including 35,366 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 0.67 (35366 hom., cov: 33)
• Consequence: RGS8 NM_001102450.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS8	NM_001102450.3	c.194-3460C>T		intron_variant		ENST00000515211.2	NP_001095920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS8	ENST00000515211.2	c.194-3460C>T		intron_variant		4	NM_001102450.3	ENSP00000511884	P1

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102579 AN: 151968 Hom.: 35368 Cov.: 33

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.737

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.664

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

GnomAD4 genome AF: 0.675 AC: 102600 AN: 152086 Hom.: 35366 Cov.: 33 AF XY: 0.675 AC XY: 50166 AN XY: 74352

Gnomad4 AFR AF: 0.534

Gnomad4 AMR AF: 0.646

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.607

Gnomad4 SAS AF: 0.737

Gnomad4 FIN AF: 0.779

Gnomad4 NFE AF: 0.753

Gnomad4 OTH AF: 0.665

Alfa AF: 0.711 Hom.: 4869

Bravo AF: 0.653

Asia WGS AF: 0.697 AC: 2423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.77
DANN	Benign	0.61

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: rs3845459; hg19: chr1-182620898;