rs13063604

chr3-128085887-G-Achr3-128085887-G-Cchr3-128085887-G-T

Variant summary

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

The NM_003707.3(RUVBL1):c.1119+1819C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,170 control chromosomes in the GnomAD database, including 3,977 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 0.23 (3977 hom., cov: 33)
• Consequence: RUVBL1 NM_003707.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.828

Genes affected

RUVBL1 (HGNC:10474): (RuvB like AAA ATPase 1) This gene encodes a protein that has both DNA-dependent ATPase and DNA helicase activities and belongs to the ATPases associated with diverse cellular activities (AAA+) protein family. The encoded protein associates with several multisubunit transcriptional complexes and with protein complexes involved in both ATP-dependent remodeling and histone modification. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUVBL1	NM_003707.3	c.1119+1819C>T		intron_variant		ENST00000322623.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUVBL1	ENST00000322623.10	c.1119+1819C>T		intron_variant		1	NM_003707.3	P1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34417 AN: 152052 Hom.: 3976 Cov.: 33

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.0834

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.226 AC: 34423 AN: 152170 Hom.: 3977 Cov.: 33 AF XY: 0.227 AC XY: 16886 AN XY: 74406

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.0836

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.223

Alfa AF: 0.207 Hom.: 1052

Bravo AF: 0.216

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.29
Dann	Benign	0.72

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: rs13063604; hg19: chr3-127804730;