7-151341795-C-G

Variant names:

• chr7-151341795-C-G
• rs1464997003
• ENST00000413040.7:c.-54C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000413040.7(NUB1):​c.-54C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: NUB1 ENST00000413040.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271
• Publications: 0 publications found

Genes affected

NUB1 (HGNC:17623): (negative regulator of ubiquitin like proteins 1) This gene encodes a protein that functions as a negative regulator of NEDD8, a ubiquitin-like protein that conjugates with cullin family members in order to regulate vital biological events. The protein encoded by this gene regulates the NEDD8 conjugation system post-transcriptionally by recruiting NEDD8 and its conjugates to the proteasome for degradation. This protein interacts with the product of the AIPL1 gene, which is associated with Leber congenital amaurosis, an inherited retinopathy, and mutations in that gene can abolish interaction with this protein, which may contribute to the pathogenesis. This protein is also known to accumulate in Lewy bodies in Parkinson's disease and dementia with Lewy bodies, and in glial cytoplasmic inclusions in multiple system atrophy, with this abnormal accumulation being specific to alpha-synucleinopathy lesions. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07703298).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUB1	NM_001243351.2	c.-54C>G		upstream_gene_variant		ENST00000568733.6	NP_001230280.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUB1	ENST00000413040.7	c.-54C>G		5_prime_UTR_variant	Exon 1 of 15	1		ENSP00000398644.3
NUB1	ENST00000568733.6	c.-54C>G		upstream_gene_variant		1	NM_001243351.2	ENSP00000454264.2
NUB1	ENST00000470229.6	c.-173C>G		upstream_gene_variant		2		ENSP00000418234.2
NUB1	ENST00000468404.5	n.-54C>G		upstream_gene_variant		5		ENSP00000420638.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	1.9
DANN	Benign	0.66
DEOGEN2	Benign	0.0050	T;T
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.33	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.077	T;T
PhyloP100		-0.27
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.11	N;N
Sift	Benign	0.59	T;T
Vest4		0.12
MVP		0.61
MPC		0.35
GERP RS		0.99
PromoterAI		-0.13	Neutral
gMVP		0.34

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: rs1464997003; hg19: chr7-151038881;