Genetic Variant NM_006666.3:c.1251+77C>T (chr19-49015227-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006666.3(RUVBL2):c.1251+77C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 1,549,206 control chromosomes in the GnomAD database, including 187,036 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 0.47 ( 17177 hom., cov: 33)

Exomes 𝑓: 0.49 ( 169859 hom. )

Consequence

RUVBL2
NM_006666.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.386

Publications

22 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RUVBL2	NM_006666.3 link	c.1251+77C>T	intron_variant	Intron 13 of 14	ENST00000595090.6	NP_006657.1	Q9Y230-1
RUVBL2	NM_001321190.2 link	c.1149+77C>T	intron_variant	Intron 13 of 14		NP_001308119.1	B3KNL2
RUVBL2	NM_001321191.1 link	c.1116+77C>T	intron_variant	Intron 13 of 14		NP_001308120.1	Q9Y230-2
RUVBL2	NR_135578.2 link	n.1265+77C>T	intron_variant	Intron 13 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUVBL2	ENST00000595090.6 link	c.1251+77C>T		intron_variant	Intron 13 of 14	1	NM_006666.3	ENSP00000473172.1		Q9Y230-1

Frequencies

GnomAD3 genomes

AF:

0.471

AC:

71582

AN:

151960

Hom.:

17162

Cov.:

show subpopulations

Gnomad AFR

AF:

0.411

Gnomad AMI

AF:

0.541

Gnomad AMR

AF:

0.560

Gnomad ASJ

AF:

0.488

Gnomad EAS

AF:

0.275

Gnomad SAS

AF:

0.492

Gnomad FIN

AF:

0.479

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.499

Gnomad OTH

AF:

0.448

GnomAD4 exome

AF:

0.490

AC:

685028

AN:

1397128

Hom.:

169859

Cov.:

AF XY:

0.490

AC XY:

339500

AN XY:

692646

show subpopulations

African (AFR)

AF:

0.413

AC:

12890

AN:

31244

American (AMR)

AF:

0.631

AC:

26887

AN:

42634

Ashkenazi Jewish (ASJ)

AF:

0.505

AC:

12592

AN:

24938

East Asian (EAS)

AF:

0.290

AC:

10371

AN:

35808

South Asian (SAS)

AF:

0.493

AC:

39384

AN:

79910

European-Finnish (FIN)

AF:

0.486

AC:

18493

AN:

38022

Middle Eastern (MID)

AF:

0.508

AC:

2790

AN:

5492

European-Non Finnish (NFE)

AF:

0.494

AC:

533732

AN:

1081108

Other (OTH)

AF:

0.481

AC:

27889

AN:

57972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

17544

35088

52633

70177

87721

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15592

31184

46776

62368

77960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.471

AC:

71622

AN:

152078

Hom.:

17177

Cov.:

AF XY:

0.472

AC XY:

35074

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.411

AC:

17029

AN:

41474

American (AMR)

AF:

0.560

AC:

8573

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.488

AC:

1694

AN:

3472

East Asian (EAS)

AF:

0.274

AC:

1417

AN:

5170

South Asian (SAS)

AF:

0.493

AC:

2383

AN:

4830

European-Finnish (FIN)

AF:

0.479

AC:

5057

AN:

10554

Middle Eastern (MID)

AF:

0.490

AC:

144

AN:

294

European-Non Finnish (NFE)

AF:

0.499

AC:

33896

AN:

67968

Other (OTH)

AF:

0.444

AC:

938

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

2033

4067

6100

8134

10167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

650

1300

1950

2600

3250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.487

Hom.:

57272

Bravo

AF:

0.468

Asia WGS

AF:

0.355

AC:

1237

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

6.2

(source)

DANN

Benign

0.80

PhyloP100

-0.39

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over