rs11158609

Positions:

• chr14-24219608-G-A

Variant summary

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

The NM_006156.3(NEDD8):​c.19-1177C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.888 in 151,996 control chromosomes in the GnomAD database, including 60,001 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 0.89 (60001 hom., cov: 29)
• Consequence: NEDD8 NM_006156.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840

Genes affected

NEDD8 (HGNC:7732): (NEDD8 ubiquitin like modifier) Enables ubiquitin protein ligase binding activity. Acts upstream of or within protein neddylation. Located in cytosol and nucleoplasm. Biomarker of Parkinson's disease and malignant astrocytoma. [provided by Alliance of Genome Resources, Apr 2022]

NEDD8-MDP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEDD8	NM_006156.3	c.19-1177C>T		intron_variant		ENST00000250495.10
NEDD8-MDP1	NR_137631.2	n.119-1177C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEDD8	ENST00000250495.10	c.19-1177C>T		intron_variant		1	NM_006156.3	P1

Frequencies

GnomAD3 genomes AF: 0.888 AC: 134822 AN: 151878 Hom.: 59937 Cov.: 29

Gnomad AFR AF: 0.922

Gnomad AMI AF: 0.929

Gnomad AMR AF: 0.918

Gnomad ASJ AF: 0.925

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.859

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.894

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

GnomAD4 genome AF: 0.888 AC: 134945 AN: 151996 Hom.: 60001 Cov.: 29 AF XY: 0.886 AC XY: 65804 AN XY: 74266

Gnomad4 AFR AF: 0.922

Gnomad4 AMR AF: 0.918

Gnomad4 ASJ AF: 0.925

Gnomad4 EAS AF: 0.898

Gnomad4 SAS AF: 0.859

Gnomad4 FIN AF: 0.823

Gnomad4 NFE AF: 0.869

Gnomad4 OTH AF: 0.896

Alfa AF: 0.885 Hom.: 35695

Bravo AF: 0.899

Asia WGS AF: 0.900 AC: 3129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.83
DANN	Benign	0.48

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: rs11158609; hg19: chr14-24688814;