Variant 19-49010016-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_006666.3(RUVBL2):c.613C>T(p.Leu205=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 1,589,768 control chromosomes in the GnomAD database, including 181,568 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 0.42 ( 14424 hom., cov: 32)

Exomes 𝑓: 0.48 ( 167144 hom. )

Consequence

RUVBL2
NM_006666.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.44

Variant links:

Genes affected

RUVBL2 (HGNC:10475): (RuvB like AAA ATPase 2) This gene encodes the second human homologue of the bacterial RuvB gene. Bacterial RuvB protein is a DNA helicase essential for homologous recombination and DNA double-strand break repair. Functional analysis showed that this gene product has both ATPase and DNA helicase activities. This gene is physically linked to the CGB/LHB gene cluster on chromosome 19q13.3, and is very close (55 nt) to the LHB gene, in the opposite orientation. [provided by RefSeq, Jul 2008]

RUVBL2 links:

MIR6798 (HGNC:50013): (microRNA 6798) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR6798 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP7

Synonymous conserved (PhyloP=2.44 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUVBL2	NM_006666.3 linkuse as main transcript	c.613C>T	p.Leu205=	synonymous_variant	8/15	ENST00000595090.6	NP_006657.1
MIR6798	NR_106856.1 linkuse as main transcript			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUVBL2	ENST00000595090.6 linkuse as main transcript	c.613C>T	p.Leu205=	synonymous_variant	8/15	1	NM_006666.3	ENSP00000473172	P1	Q9Y230-1
MIR6798	ENST00000612887.1 linkuse as main transcript			downstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.419

AC:

63719

AN:

151904

Hom.:

14422

Cov.:

show subpopulations

Gnomad AFR

AF:

0.242

Gnomad AMI

AF:

0.594

Gnomad AMR

AF:

0.479

Gnomad ASJ

AF:

0.543

Gnomad EAS

AF:

0.413

Gnomad SAS

AF:

0.467

Gnomad FIN

AF:

0.469

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.495

Gnomad OTH

AF:

0.419

GnomAD3 exomes

AF:

0.480

AC:

112028

AN:

233248

Hom.:

27761

AF XY:

0.483

AC XY:

60899

AN XY:

126204

show subpopulations

Gnomad AFR exome

AF:

0.236

Gnomad AMR exome

AF:

0.587

Gnomad ASJ exome

AF:

0.563

Gnomad EAS exome

AF:

0.402

Gnomad SAS exome

AF:

0.472

Gnomad FIN exome

AF:

0.474

Gnomad NFE exome

AF:

0.493

Gnomad OTH exome

AF:

0.482

GnomAD4 exome

AF:

0.479

AC:

689091

AN:

1437744

Hom.:

167144

Cov.:

AF XY:

0.480

AC XY:

341952

AN XY:

712516

show subpopulations

Gnomad4 AFR exome

AF:

0.237

Gnomad4 AMR exome

AF:

0.567

Gnomad4 ASJ exome

AF:

0.558

Gnomad4 EAS exome

AF:

0.426

Gnomad4 SAS exome

AF:

0.470

Gnomad4 FIN exome

AF:

0.472

Gnomad4 NFE exome

AF:

0.485

Gnomad4 OTH exome

AF:

0.467

GnomAD4 genome

AF:

0.419

AC:

63722

AN:

152024

Hom.:

14424

Cov.:

AF XY:

0.420

AC XY:

31236

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.242

Gnomad4 AMR

AF:

0.478

Gnomad4 ASJ

AF:

0.543

Gnomad4 EAS

AF:

0.412

Gnomad4 SAS

AF:

0.467

Gnomad4 FIN

AF:

0.469

Gnomad4 NFE

AF:

0.495

Gnomad4 OTH

AF:

0.416

Alfa

AF:

0.463

Hom.:

15923

Bravo

AF:

0.411

Asia WGS

AF:

0.371

AC:

1294

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.86

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over