3-128093194-C-T

Variant names:

• chr3-128093194-C-T
• rs13091198
• NM_003707.3:c.1016+4106G>A

Variant summary

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

The NM_003707.3(RUVBL1):​c.1016+4106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,154 control chromosomes in the GnomAD database, including 1,634 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 0.14 (1634 hom., cov: 32)
• Consequence: RUVBL1 NM_003707.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.286
• Publications: 8 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 (AFR) allele frequency at 95% confidence interval = 0.199 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.1016+4106G>A		intron	N/A	NP_003698.1
	RUVBL1	NM_001319084.2		c.1016+4106G>A		intron	N/A	NP_001306013.1
	RUVBL1	NM_001319086.1		c.836+4106G>A		intron	N/A	NP_001306015.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUVBL1	ENST00000322623.10	TSL:1 MANE Select	c.1016+4106G>A		intron	N/A	ENSP00000318297.5
	RUVBL1	ENST00000881252.1		c.1017-1612G>A		intron	N/A	ENSP00000551311.1
	RUVBL1	ENST00000931764.1		c.1017-1612G>A		intron	N/A	ENSP00000601823.1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21107 AN: 152036 Hom.: 1635 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.00461

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.139 AC: 21106 AN: 152154 Hom.: 1634 Cov.: 32 AF XY: 0.137 AC XY: 10229 AN XY: 74402

African (AFR) AF: 0.202 AC: 8384 AN: 41472

American (AMR) AF: 0.106 AC: 1620 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 412 AN: 3468

East Asian (EAS) AF: 0.00462 AC: 24 AN: 5190

South Asian (SAS) AF: 0.181 AC: 874 AN: 4824

European-Finnish (FIN) AF: 0.109 AC: 1151 AN: 10584

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8183 AN: 68008

Other (OTH) AF: 0.125 AC: 264 AN: 2116

Alfa AF: 0.138 Hom.: 207

Bravo AF: 0.137

Asia WGS AF: 0.0840 AC: 294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	6.8
DANN	Benign	0.70
PhyloP100		-0.29
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: rs13091198; hg19: chr3-127812037;