3-128103477-T-C

Position:

• chr3-128103477-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003707.3(RUVBL1):​c.513+1296A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 152,132 control chromosomes in the GnomAD database, including 39,322 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 0.72 (39322 hom., cov: 33)
• Consequence: RUVBL1 NM_003707.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUVBL1	NM_003707.3	c.513+1296A>G		intron_variant		ENST00000322623.10	NP_003698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUVBL1	ENST00000322623.10	c.513+1296A>G		intron_variant		1	NM_003707.3	ENSP00000318297.5
RUVBL1	ENST00000464873.5	c.333+1296A>G		intron_variant		2		ENSP00000420738.1

Frequencies

GnomAD3 genomes AF: 0.717 AC: 109055 AN: 152014 Hom.: 39278 Cov.: 33

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.735

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

GnomAD4 genome AF: 0.718 AC: 109157 AN: 152132 Hom.: 39322 Cov.: 33 AF XY: 0.716 AC XY: 53207 AN XY: 74360

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.692

Gnomad4 ASJ AF: 0.694

Gnomad4 EAS AF: 0.888

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.721

Gnomad4 NFE AF: 0.726

Gnomad4 OTH AF: 0.739

Alfa AF: 0.710 Hom.: 19681

Bravo AF: 0.724

Asia WGS AF: 0.770 AC: 2677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	16
DANN	Benign	0.85

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: rs7641133; hg19: chr3-127822320; COSMIC: COSV59475359; COSMIC: COSV59475359;