rs17599948

Positions:

• chr17-43201393-A-G

Variant summary

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

The NM_005899.5(NBR1):​c.2469-293A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,266 control chromosomes in the GnomAD database, including 2,024 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 0.15 (2024 hom., cov: 32)
• Consequence: NBR1 NM_005899.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NBR1	NM_005899.5	c.2469-293A>G		intron_variant		ENST00000590996.6	NP_005890.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NBR1	ENST00000590996.6	c.2469-293A>G		intron_variant		1	NM_005899.5	ENSP00000466667	P1
NBR1	ENST00000341165.10	c.2469-293A>G		intron_variant		1		ENSP00000343479	P1
NBR1	ENST00000589872.1	c.2469-293A>G		intron_variant		1		ENSP00000467816
NBR1	ENST00000542611.5	c.2406-293A>G		intron_variant		2		ENSP00000437545

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23376 AN: 152148 Hom.: 2021 Cov.: 32

Gnomad AFR AF: 0.0917

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0911

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.154 AC: 23385 AN: 152266 Hom.: 2024 Cov.: 32 AF XY: 0.158 AC XY: 11773 AN XY: 74444

Gnomad4 AFR AF: 0.0915

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.0909

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.172

Alfa AF: 0.168 Hom.: 3872

Bravo AF: 0.147

Asia WGS AF: 0.215 AC: 749 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.89
DANN	Benign	0.46

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: rs17599948; hg19: chr17-41353410;