rs3783197

Positions:

• chr13-41469534-G-A
• chr13-41469534-G-T

Variant summary

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

The NM_014059.3(RGCC):​c.406+696G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,938 control chromosomes in the GnomAD database, including 14,336 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 0.40 (14336 hom., cov: 30)
• Consequence: RGCC NM_014059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.655

Genes affected

RGCC (HGNC:20369): (regulator of cell cycle) This gene is thought to regulate cell cycle progression. It is induced by p53 in response to DNA damage, or by sublytic levels of complement system proteins that result in activation of the cell cycle. The encoded protein localizes to the cytoplasm during interphase and to centrosomes during mitosis. The protein forms a complex with polo-like kinase 1. The protein also translocates to the nucleus in response to treatment with complement system proteins, and can associate with and increase the kinase activity of cell division cycle 2 protein. In different assays and cell types, overexpression of this protein has been shown to activate or suppress cell cycle progression. [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 (SAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGCC	NM_014059.3	c.406+696G>A		intron_variant		ENST00000379359.4	NP_054778.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGCC	ENST00000379359.4	c.406+696G>A		intron_variant		1	NM_014059.3	ENSP00000368664.3

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61343 AN: 151820 Hom.: 14332 Cov.: 30

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.404 AC: 61356 AN: 151938 Hom.: 14336 Cov.: 30 AF XY: 0.413 AC XY: 30686 AN XY: 74242

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.524

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.562

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.417

Alfa AF: 0.488 Hom.: 38429

Bravo AF: 0.376

Asia WGS AF: 0.494 AC: 1717 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	0.34
DANN	Benign	0.68

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: rs3783197; hg19: chr13-42043670;