19-48993898-A-G

Variant names:

• chr19-48993898-A-G
• rs3764618
• NM_006666.3:c.-14A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006666.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUVBL2	NM_006666.3	MANE Select	c.-14A>G		5_prime_UTR	Exon 1 of 15	NP_006657.1
	RUVBL2	NR_135578.2		n.12A>G		non_coding_transcript_exon	Exon 1 of 15
	RUVBL2	NM_001321190.2		c.-186A>G		5_prime_UTR	Exon 1 of 15	NP_001308119.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUVBL2	ENST00000595090.6	TSL:1 MANE Select	c.-14A>G		5_prime_UTR	Exon 1 of 15	ENSP00000473172.1
	RUVBL2	ENST00000594017.5	TSL:2	n.9A>G		non_coding_transcript_exon	Exon 1 of 8
	RUVBL2	ENST00000595811.5	TSL:5	n.-14A>G		non_coding_transcript_exon	Exon 1 of 6	ENSP00000469760.1

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

GnomAD2 exomes AF: 0.0903 AC: 22471 AN: 248892 AF XY: 0.0835

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 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

African (AFR) AF: 0.0960 AC: 3214 AN: 33478

American (AMR) AF: 0.150 AC: 6686 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.0560 AC: 1463 AN: 26132

East Asian (EAS) AF: 0.0764 AC: 3033 AN: 39688

South Asian (SAS) AF: 0.0326 AC: 2810 AN: 86252

European-Finnish (FIN) AF: 0.138 AC: 7383 AN: 53390

Middle Eastern (MID) AF: 0.0600 AC: 346 AN: 5766

European-Non Finnish (NFE) AF: 0.0746 AC: 82974 AN: 1111644

Other (OTH) AF: 0.0771 AC: 4658 AN: 60384

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

African (AFR) AF: 0.0974 AC: 4042 AN: 41508

American (AMR) AF: 0.124 AC: 1890 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0611 AC: 212 AN: 3468

East Asian (EAS) AF: 0.0770 AC: 398 AN: 5166

South Asian (SAS) AF: 0.0320 AC: 154 AN: 4816

European-Finnish (FIN) AF: 0.136 AC: 1438 AN: 10572

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0791 AC: 5380 AN: 68004

Other (OTH) AF: 0.0928 AC: 196 AN: 2112

Alfa AF: 0.0786 Hom.: 934

Bravo AF: 0.0917

Asia WGS AF: 0.0710 AC: 249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Benign	0.74
PhyloP100		1.2
PromoterAI		0.031	Neutral
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3764618; hg19: chr19-49497155; COSMIC: COSV107207530; COSMIC: COSV107207530;