rs7650365

Positions:

• chr3-128115160-G-A

Variant summary

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

The NM_003707.3(RUVBL1):​c.229-2140C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 151,946 control chromosomes in the GnomAD database, including 11,494 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 0.35 (11494 hom., cov: 31)
• Consequence: RUVBL1 NM_003707.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.359

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUVBL1	NM_003707.3	c.229-2140C>T		intron_variant		ENST00000322623.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUVBL1	ENST00000322623.10	c.229-2140C>T		intron_variant		1	NM_003707.3	P1
RUVBL1	ENST00000464873.5	c.49-2140C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53501 AN: 151828 Hom.: 11497 Cov.: 31

Gnomad AFR AF: 0.0916

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.352 AC: 53499 AN: 151946 Hom.: 11494 Cov.: 31 AF XY: 0.353 AC XY: 26205 AN XY: 74264

Gnomad4 AFR AF: 0.0914

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.486

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.391

Alfa AF: 0.456 Hom.: 32369

Bravo AF: 0.341

Asia WGS AF: 0.350 AC: 1218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.83

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: rs7650365; hg19: chr3-127834003; COSMIC: COSV59475368;