rs753307

Positions:

• chr19-49015227-C-T

Variant summary

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

The ENST00000595090.6(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 ENST00000595090.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.386

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUVBL2	NM_006666.3	c.1251+77C>T		intron_variant		ENST00000595090.6	NP_006657.1
RUVBL2	NM_001321190.2	c.1149+77C>T		intron_variant			NP_001308119.1
RUVBL2	NM_001321191.1	c.1116+77C>T		intron_variant			NP_001308120.1
RUVBL2	NR_135578.2	n.1265+77C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUVBL2	ENST00000595090.6	c.1251+77C>T		intron_variant		1	NM_006666.3	ENSP00000473172	P1

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71582 AN: 151960 Hom.: 17162 Cov.: 33

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.: 26 AF XY: 0.490 AC XY: 339500 AN XY: 692646

Gnomad4 AFR exome AF: 0.413

Gnomad4 AMR exome AF: 0.631

Gnomad4 ASJ exome AF: 0.505

Gnomad4 EAS exome AF: 0.290

Gnomad4 SAS exome AF: 0.493

Gnomad4 FIN exome AF: 0.486

Gnomad4 NFE exome AF: 0.494

Gnomad4 OTH exome AF: 0.481

GnomAD4 genome AF: 0.471 AC: 71622 AN: 152078 Hom.: 17177 Cov.: 33 AF XY: 0.472 AC XY: 35074 AN XY: 74322

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.560

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.444

Alfa AF: 0.492 Hom.: 35651

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
DANN	Benign	0.80

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

LitVar

Other links and lift over

dbSNP: rs753307; hg19: chr19-49518484; COSMIC: COSV55487122; COSMIC: COSV55487122;