rs13119

Positions:

• chr17-43210702-C-T

Variant summary

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

The ENST00000590996.6(NBR1):​c.*628C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 398,180 control chromosomes in the GnomAD database, including 21,580 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 0.30 (7520 hom., cov: 32)
  • Exomes 𝑓: 0.34 (14060 hom.)
• Consequence: NBR1 ENST00000590996.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.506

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NBR1	NM_005899.5	c.*628C>T		3_prime_UTR_variant	21/21	ENST00000590996.6	NP_005890.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NBR1	ENST00000590996.6	c.*628C>T		3_prime_UTR_variant	21/21	1	NM_005899.5	ENSP00000466667	P1
NBR1	ENST00000341165.10	c.*628C>T		3_prime_UTR_variant	21/21	1		ENSP00000343479	P1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 45975 AN: 151854 Hom.: 7521 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.323

GnomAD4 exome AF: 0.336 AC: 82660 AN: 246208 Hom.: 14060 Cov.: 0 AF XY: 0.337 AC XY: 42030 AN XY: 124750

Gnomad4 AFR exome AF: 0.174

Gnomad4 AMR exome AF: 0.337

Gnomad4 ASJ exome AF: 0.353

Gnomad4 EAS exome AF: 0.340

Gnomad4 SAS exome AF: 0.505

Gnomad4 FIN exome AF: 0.394

Gnomad4 NFE exome AF: 0.330

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.302 AC: 45971 AN: 151972 Hom.: 7520 Cov.: 32 AF XY: 0.309 AC XY: 22966 AN XY: 74292

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.406

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.327

Alfa AF: 0.317 Hom.: 1609

Bravo AF: 0.286

Asia WGS AF: 0.404 AC: 1405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.3
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: rs13119; hg19: chr17-41362721;