chr19-49015318-A-G

Position:

• chr19-49015318-A-G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.653

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUVBL2	NM_006666.3	c.1251+168A>G		intron_variant		ENST00000595090.6
RUVBL2	NM_001321190.2	c.1149+168A>G		intron_variant
RUVBL2	NM_001321191.1	c.1116+168A>G		intron_variant
RUVBL2	NR_135578.2	n.1265+168A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUVBL2	ENST00000595090.6	c.1251+168A>G		intron_variant		1	NM_006666.3	P1

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102919 AN: 152006 Hom.: 36528 Cov.: 33

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.: 9 AF XY: 0.587 AC XY: 215011 AN XY: 366342

Gnomad4 AFR exome AF: 0.904

Gnomad4 AMR exome AF: 0.711

Gnomad4 ASJ exome AF: 0.573

Gnomad4 EAS exome AF: 0.346

Gnomad4 SAS exome AF: 0.550

Gnomad4 FIN exome AF: 0.631

Gnomad4 NFE exome AF: 0.587

Gnomad4 OTH exome AF: 0.601

GnomAD4 genome AF: 0.677 AC: 103021 AN: 152124 Hom.: 36576 Cov.: 33 AF XY: 0.675 AC XY: 50155 AN XY: 74358

Gnomad4 AFR AF: 0.895

Gnomad4 AMR AF: 0.694

Gnomad4 ASJ AF: 0.560

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.631

Alfa AF: 0.665 Hom.: 6210

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
DANN	Benign	0.68

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

LitVar

Other links and lift over

dbSNP: rs753308; hg19: chr19-49518575; COSMIC: COSV55487831; COSMIC: COSV55487831;