rs3764618

chr19-48993898-A-Gchr19-48993898-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006666.3(RUVBL2):c.-14A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0783 in 1,613,558 control chromosomes in the GnomAD database, including 5,504 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 0.091 (668 hom., cov: 31)
  • Exomes 𝑓: 0.077 (4836 hom.)
• Consequence: RUVBL2 NM_006666.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUVBL2	NM_006666.3	c.-14A>G		5_prime_UTR_variant	1/15	ENST00000595090.6
RUVBL2	NM_001321190.2	c.-186A>G		5_prime_UTR_variant	1/15
RUVBL2	NM_001321191.1	c.-128A>G		5_prime_UTR_variant	1/15
RUVBL2	NR_135578.2	n.12A>G		non_coding_transcript_exon_variant	1/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUVBL2	ENST00000595090.6	c.-14A>G		5_prime_UTR_variant	1/15	1	NM_006666.3	P1

Frequencies

GnomAD3 genomes AF: 0.0909 AC: 13811 AN: 152010 Hom.: 665 Cov.: 31

Gnomad AFR AF: 0.0970

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0611

Gnomad EAS AF: 0.0765

Gnomad SAS AF: 0.0324

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0791

Gnomad OTH AF: 0.0914

GnomAD3 exomes AF: 0.0903 AC: 22471 AN: 248892 Hom.: 1179 AF XY: 0.0835 AC XY: 11297 AN XY: 135286

Gnomad AFR exome AF: 0.0951

Gnomad AMR exome AF: 0.157

Gnomad ASJ exome AF: 0.0547

Gnomad EAS exome AF: 0.0852

Gnomad SAS exome AF: 0.0345

Gnomad FIN exome AF: 0.138

Gnomad NFE exome AF: 0.0797

Gnomad OTH exome AF: 0.0839

GnomAD4 exome AF: 0.0770 AC: 112567 AN: 1461430 Hom.: 4836 Cov.: 32 AF XY: 0.0756 AC XY: 54984 AN XY: 727056

Gnomad4 AFR exome AF: 0.0960

Gnomad4 AMR exome AF: 0.150

Gnomad4 ASJ exome AF: 0.0560

Gnomad4 EAS exome AF: 0.0764

Gnomad4 SAS exome AF: 0.0326

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.0746

Gnomad4 OTH exome AF: 0.0771

GnomAD4 genome AF: 0.0910 AC: 13843 AN: 152128 Hom.: 668 Cov.: 31 AF XY: 0.0923 AC XY: 6860 AN XY: 74358

Gnomad4 AFR AF: 0.0974

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.0611

Gnomad4 EAS AF: 0.0770

Gnomad4 SAS AF: 0.0320

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.0791

Gnomad4 OTH AF: 0.0928

Alfa AF: 0.0663 Hom.: 188

Bravo AF: 0.0917

Asia WGS AF: 0.0710 AC: 249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	18
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: 0

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

Publications

LitVar

Other links and lift over

dbSNP: rs3764618; hg19: chr19-49497155;