3-128080312-A-G

Position:

• chr3-128080312-A-G

Variant summary

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

The NM_001319086.1(RUVBL1):​c.939+7394T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0894 in 152,252 control chromosomes in the GnomAD database, including 780 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 0.089 (780 hom., cov: 33)
• Consequence: RUVBL1 NM_001319086.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.520

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUVBL1	NM_001319086.1	c.939+7394T>C		intron_variant			NP_001306015.1
RUVBL1	XM_011513248.3	c.*44+7394T>C		intron_variant			XP_011511550.1
RUVBL1	XM_011513249.4	c.1119+7394T>C		intron_variant			XP_011511551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUVBL1	ENST00000464873.5	c.939+7394T>C		intron_variant		2		ENSP00000420738
RUVBL1	ENST00000472125.5	c.475-15092T>C		intron_variant		3		ENSP00000417370
RUVBL1	ENST00000585057.5	c.392+2171T>C		intron_variant, NMD_transcript_variant		3		ENSP00000463669

Frequencies

GnomAD3 genomes AF: 0.0894 AC: 13606 AN: 152134 Hom.: 780 Cov.: 33

Gnomad AFR AF: 0.0206

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.0633

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.0792

Gnomad SAS AF: 0.0909

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.0963

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

GnomAD4 genome AF: 0.0894 AC: 13613 AN: 152252 Hom.: 780 Cov.: 33 AF XY: 0.0912 AC XY: 6788 AN XY: 74452

Gnomad4 AFR AF: 0.0206

Gnomad4 AMR AF: 0.0631

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.0794

Gnomad4 SAS AF: 0.0912

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.0991

Alfa AF: 0.116 Hom.: 1554

Bravo AF: 0.0813

Asia WGS AF: 0.0960 AC: 336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.48
DANN	Benign	0.49

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9860614; hg19: chr3-127799155;