rs11719889

Positions:

• chr3-128086937-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.1119+769C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,192 control chromosomes in the GnomAD database, including 4,061 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 (4061 hom., cov: 33)
• Consequence: RUVBL1 NM_003707.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.876

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUVBL1	NM_003707.3	c.1119+769C>T		intron_variant		ENST00000322623.10	NP_003698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUVBL1	ENST00000322623.10	c.1119+769C>T		intron_variant		1	NM_003707.3	ENSP00000318297	P1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34828 AN: 152072 Hom.: 4061 Cov.: 33

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.0837

Gnomad SAS AF: 0.269

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: 0.229 AC: 34833 AN: 152192 Hom.: 4061 Cov.: 33 AF XY: 0.229 AC XY: 17055 AN XY: 74402

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.0839

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.224

Alfa AF: 0.236 Hom.: 561

Bravo AF: 0.219

Asia WGS AF: 0.179 AC: 625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.94

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: rs11719889; hg19: chr3-127805780;