rs10916583

Positions:

• chr1-224299364-T-C

Variant summary

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

The ENST00000281701.11(NVL):​c.1062+1198A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,160 control chromosomes in the GnomAD database, including 1,605 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 0.12 (1605 hom., cov: 32)
• Consequence: NVL ENST00000281701.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.25

Genes affected

NVL (HGNC:8070): (nuclear VCP like) This gene encodes a member of the AAA (ATPases associated with diverse cellular activities) superfamily. Multiple transcript variants encoding different isoforms have been found for this gene. Two encoded proteins, described as major and minor isoforms, have been localized to distinct regions of the nucleus. The largest encoded protein (major isoform) has been localized to the nucleolus and shown to participate in ribosome biosynthesis (PMID: 15469983, 16782053), while the minor isoform has been localized to the nucleoplasmin. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NVL	NM_002533.4	c.1062+1198A>G		intron_variant		ENST00000281701.11	NP_002524.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NVL	ENST00000281701.11	c.1062+1198A>G		intron_variant		1	NM_002533.4	ENSP00000281701	P1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17953 AN: 152042 Hom.: 1598 Cov.: 32

Gnomad AFR AF: 0.0270

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.118 AC: 17960 AN: 152160 Hom.: 1605 Cov.: 32 AF XY: 0.125 AC XY: 9269 AN XY: 74384

Gnomad4 AFR AF: 0.0269

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.123

Alfa AF: 0.113 Hom.: 214

Bravo AF: 0.114

Asia WGS AF: 0.238 AC: 826 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.23
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs10916583; hg19: chr1-224487066;