Variant 19-49015801-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006666.3(RUVBL2):c.1367-16T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 1,613,232 control chromosomes in the GnomAD database, including 280,359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 30424 hom., cov: 32)

Exomes 𝑓: 0.58 ( 249935 hom. )

Consequence

RUVBL2
NM_006666.3 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0660

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 19-49015801-T-C is Benign according to our data. Variant chr19-49015801-T-C is described in ClinVar as [Benign]. Clinvar id is 1277510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
RUVBL2	NM_006666.3 linkuse as main transcript	c.1367-16T>C	splice_polypyrimidine_tract_variant, intron_variant	ENST00000595090.6
RUVBL2	NM_001321190.2 linkuse as main transcript	c.1265-16T>C	splice_polypyrimidine_tract_variant, intron_variant
RUVBL2	NM_001321191.1 linkuse as main transcript	c.1232-16T>C	splice_polypyrimidine_tract_variant, intron_variant
RUVBL2	NR_135578.2 linkuse as main transcript	n.1381-16T>C	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUVBL2	ENST00000595090.6 linkuse as main transcript	c.1367-16T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_006666.3	P1	Q9Y230-1

Frequencies

GnomAD3 genomes

AF:

0.627

AC:

95252

AN:

151970

Hom.:

30392

Cov.:

show subpopulations

Gnomad AFR

AF:

0.722

Gnomad AMI

AF:

0.655

Gnomad AMR

AF:

0.668

Gnomad ASJ

AF:

0.561

Gnomad EAS

AF:

0.332

Gnomad SAS

AF:

0.544

Gnomad FIN

AF:

0.620

Gnomad MID

AF:

0.671

Gnomad NFE

AF:

0.593

Gnomad OTH

AF:

0.597

GnomAD3 exomes

AF:

0.592

AC:

147970

AN:

249866

Hom.:

45050

AF XY:

0.585

AC XY:

79236

AN XY:

135544

show subpopulations

Gnomad AFR exome

AF:

0.727

Gnomad AMR exome

AF:

0.706

Gnomad ASJ exome

AF:

0.566

Gnomad EAS exome

AF:

0.326

Gnomad SAS exome

AF:

0.548

Gnomad FIN exome

AF:

0.627

Gnomad NFE exome

AF:

0.590

Gnomad OTH exome

AF:

0.586

GnomAD4 exome

AF:

0.582

AC:

849875

AN:

1461144

Hom.:

249935

Cov.:

AF XY:

0.580

AC XY:

421754

AN XY:

726920

show subpopulations

Gnomad4 AFR exome

AF:

0.735

Gnomad4 AMR exome

AF:

0.700

Gnomad4 ASJ exome

AF:

0.571

Gnomad4 EAS exome

AF:

0.342

Gnomad4 SAS exome

AF:

0.548

Gnomad4 FIN exome

AF:

0.629

Gnomad4 NFE exome

AF:

0.581

Gnomad4 OTH exome

AF:

0.583

GnomAD4 genome

AF:

0.627

AC:

95330

AN:

152088

Hom.:

30424

Cov.:

AF XY:

0.626

AC XY:

46539

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.722

Gnomad4 AMR

AF:

0.668

Gnomad4 ASJ

AF:

0.561

Gnomad4 EAS

AF:

0.332

Gnomad4 SAS

AF:

0.545

Gnomad4 FIN

AF:

0.620

Gnomad4 NFE

AF:

0.593

Gnomad4 OTH

AF:

0.594

Alfa

AF:

0.621

Hom.:

3500

Bravo

AF:

0.629

Asia WGS

AF:

0.449

AC:

1565

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.72

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over