rs8482

chr17-43209941-A-Cchr17-43209941-A-Gchr17-43209941-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005899.5(NBR1):c.2768A>C(p.His923Pro) variant causes a missense change. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H923Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 29)
• Consequence: NBR1 NM_005899.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.21

Genes affected

NBR1 (HGNC:6746): (NBR1 autophagy cargo receptor) The protein encoded by this gene was originally identified as an ovarian tumor antigen monitored in ovarian cancer. The encoded protein contains a B-box/coiled-coil motif, which is present in many genes with transformation potential. It functions as a specific autophagy receptor for the selective autophagic degradation of peroxisomes by forming intracellular inclusions with ubiquitylated autophagic substrates. This gene is located on a region of chromosome 17q21.1 that is in close proximity to the BRCA1 tumor suppressor gene. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40088332).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBR1	NM_005899.5	c.2768A>C	p.His923Pro	missense_variant	21/21	ENST00000590996.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBR1	ENST00000590996.6	c.2768A>C	p.His923Pro	missense_variant	21/21	1	NM_005899.5	P1
NBR1	ENST00000341165.10	c.2768A>C	p.His923Pro	missense_variant	21/21	1		P1
NBR1	ENST00000542611.5	c.*27A>C		3_prime_UTR_variant	18/18	2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
Cadd	Benign	23
Dann	Benign	0.95
DEOGEN2	Benign	0.076	T;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.40	T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.1	L;L
MutationTaster	Benign	0.78	D;D;D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.3	N;.
REVEL	Benign	0.16
Sift	Benign	0.24	T;.
Sift4G	Benign	0.23	T;T
Polyphen		0.99	D;D
Vest4		0.52
MutPred		0.43		Gain of relative solvent accessibility (P = 0.1259);Gain of relative solvent accessibility (P = 0.1259);
MVP		0.61
ClinPred		0.66	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.60
gMVP		0.37

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: rs8482; hg19: chr17-41361960;