dbSNP rs753308: RUVBL2:c.1251+168A>G (chr19-49015318-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000595090.6(RUVBL2):c.1251+168A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 862,206 control chromosomes in the GnomAD database, including 162,851 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 0.68 ( 36576 hom., cov: 33)

Exomes 𝑓: 0.59 ( 126275 hom. )

Consequence

RUVBL2
ENST00000595090.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.653

Publications

8 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:

Genome browser will be placed here

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=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000595090.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RUVBL2	NM_006666.3	MANE Select	c.1251+168A>G	intron	N/A	NP_006657.1
RUVBL2	NM_001321190.2		c.1149+168A>G	intron	N/A	NP_001308119.1
RUVBL2	NM_001321191.1		c.1116+168A>G	intron	N/A	NP_001308120.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RUVBL2	ENST00000595090.6	TSL:1 MANE Select	c.1251+168A>G	intron	N/A	ENSP00000473172.1
RUVBL2	ENST00000221413.10	TSL:1	n.*460+168A>G	intron	N/A	ENSP00000221413.6
RUVBL2	ENST00000595002.1	TSL:2	n.68A>G	non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.677

AC:

102919

AN:

152006

Hom.:

36528

Cov.:

show subpopulations

Gnomad AFR

AF:

0.895

Gnomad AMI

AF:

0.655

Gnomad AMR

AF:

0.694

Gnomad ASJ

AF:

0.560

Gnomad EAS

AF:

0.333

Gnomad SAS

AF:

0.545

Gnomad FIN

AF:

0.620

Gnomad MID

AF:

0.678

Gnomad NFE

AF:

0.592

Gnomad OTH

AF:

0.635

GnomAD4 exome

AF:

0.589

AC:

418102

AN:

710082

Hom.:

126275

Cov.:

AF XY:

0.587

AC XY:

215011

AN XY:

366342

show subpopulations

African (AFR)

AF:

0.904

AC:

15387

AN:

17014

American (AMR)

AF:

0.711

AC:

21474

AN:

30198

Ashkenazi Jewish (ASJ)

AF:

0.573

AC:

9250

AN:

16140

East Asian (EAS)

AF:

0.346

AC:

11147

AN:

32232

South Asian (SAS)

AF:

0.550

AC:

29516

AN:

53664

European-Finnish (FIN)

AF:

0.631

AC:

19564

AN:

30984

Middle Eastern (MID)

AF:

0.658

AC:

1751

AN:

2662

European-Non Finnish (NFE)

AF:

0.587

AC:

289085

AN:

492390

Other (OTH)

AF:

0.601

AC:

20928

AN:

34798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

8910

17819

26729

35638

44548

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5136

10272

15408

20544

25680

<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:

0.677

AC:

103021

AN:

152124

Hom.:

36576

Cov.:

AF XY:

0.675

AC XY:

50155

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.895

AC:

37193

AN:

41544

American (AMR)

AF:

0.694

AC:

10608

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.560

AC:

1943

AN:

3468

East Asian (EAS)

AF:

0.332

AC:

1714

AN:

5158

South Asian (SAS)

AF:

0.546

AC:

2635

AN:

4822

European-Finnish (FIN)

AF:

0.620

AC:

6557

AN:

10572

Middle Eastern (MID)

AF:

0.668

AC:

195

AN:

292

European-Non Finnish (NFE)

AF:

0.592

AC:

40247

AN:

67958

Other (OTH)

AF:

0.631

AC:

1332

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1592

3184

4776

6368

7960

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

780

1560

2340

3120

3900

<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:

0.632

Hom.:

14372

Bravo

AF:

0.686

Asia WGS

AF:

0.460

AC:

1606

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

5.7

(source)

DANN

Benign

0.68

PhyloP100

0.65

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over