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 NM_006666.3(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
NM_006666.3 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:

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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=-0.96).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RUVBL2	NM_006666.3 link	c.1251+168A>G	intron_variant	Intron 13 of 14	ENST00000595090.6	NP_006657.1	Q9Y230-1
RUVBL2	NM_001321190.2 link	c.1149+168A>G	intron_variant	Intron 13 of 14		NP_001308119.1	B3KNL2
RUVBL2	NM_001321191.1 link	c.1116+168A>G	intron_variant	Intron 13 of 14		NP_001308120.1	Q9Y230-2
RUVBL2	NR_135578.2 link	n.1265+168A>G	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+168A>G		intron_variant	Intron 13 of 14	1	NM_006666.3	ENSP00000473172.1		Q9Y230-1

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

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

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 v4.3

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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rs753308

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