rs512189

Variant names:

• chr1-182663452-G-A
• rs512189
• NM_001102450.3:c.193+2517C>T

Variant summary

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

The NM_001102450.3(RGS8):​c.193+2517C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.097 in 152,190 control chromosomes in the GnomAD database, including 1,936 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 0.097 (1936 hom., cov: 32)
• Consequence: RGS8 NM_001102450.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS8	NM_001102450.3	c.193+2517C>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.193+2517C>T		intron_variant	Intron 6 of 7	4	NM_001102450.3	ENSP00000511884.1

Frequencies

GnomAD3 genomes AF: 0.0967 AC: 14701 AN: 152072 Hom.: 1917 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0461

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.0352

Gnomad SAS AF: 0.0294

Gnomad FIN AF: 0.00933

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0153

Gnomad OTH AF: 0.0735

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

GnomAD4 genome AF: 0.0970 AC: 14761 AN: 152190 Hom.: 1936 Cov.: 32 AF XY: 0.0951 AC XY: 7078 AN XY: 74418

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.0460

Gnomad4 ASJ AF: 0.00836

Gnomad4 EAS AF: 0.0355

Gnomad4 SAS AF: 0.0296

Gnomad4 FIN AF: 0.00933

Gnomad4 NFE AF: 0.0153

Gnomad4 OTH AF: 0.0728

Alfa AF: 0.0391 Hom.: 262

Bravo AF: 0.109

Asia WGS AF: 0.0480 AC: 166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.35

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: rs512189; hg19: chr1-182632587;