3-128085887-G-A

Variant names:

• chr3-128085887-G-A
• rs13063604
• NM_003707.3:c.1119+1819C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003707.3(RUVBL1):​c.1119+1819C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,170 control chromosomes in the GnomAD database, including 3,977 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 0.23 (3977 hom., cov: 33)
• Consequence: RUVBL1 NM_003707.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.828
• Publications: 6 publications found

Genes affected

RUVBL1 (HGNC:10474): (RuvB like AAA ATPase 1) This gene encodes a protein that has both DNA-dependent ATPase and DNA helicase activities and belongs to the ATPases associated with diverse cellular activities (AAA+) protein family. The encoded protein associates with several multisubunit transcriptional complexes and with protein complexes involved in both ATP-dependent remodeling and histone modification. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003707.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUVBL1	NM_003707.3	MANE Select	c.1119+1819C>T		intron	N/A	NP_003698.1	A0A384MTR5
	RUVBL1	NM_001319084.2		c.1119+1819C>T		intron	N/A	NP_001306013.1	Q9Y265-2
	RUVBL1	NM_001319086.1		c.939+1819C>T		intron	N/A	NP_001306015.1	E7ETR0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUVBL1	ENST00000322623.10	TSL:1 MANE Select	c.1119+1819C>T		intron	N/A	ENSP00000318297.5	Q9Y265-1
	RUVBL1	ENST00000881252.1		c.1302+1819C>T		intron	N/A	ENSP00000551311.1
	RUVBL1	ENST00000931764.1		c.1224+1819C>T		intron	N/A	ENSP00000601823.1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34417 AN: 152052 Hom.: 3976 Cov.: 33

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.0834

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.222

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.226 AC: 34423 AN: 152170 Hom.: 3977 Cov.: 33 AF XY: 0.227 AC XY: 16886 AN XY: 74406

African (AFR) AF: 0.216 AC: 8975 AN: 41510

American (AMR) AF: 0.168 AC: 2566 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 929 AN: 3472

East Asian (EAS) AF: 0.0836 AC: 433 AN: 5182

South Asian (SAS) AF: 0.273 AC: 1318 AN: 4830

European-Finnish (FIN) AF: 0.262 AC: 2767 AN: 10578

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16561 AN: 67998

Other (OTH) AF: 0.223 AC: 472 AN: 2112

Alfa AF: 0.222 Hom.: 1968

Bravo AF: 0.216

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.29
DANN	Benign	0.72
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs13063604; hg19: chr3-127804730;