rs13119

Variant names:

• chr17-43210702-C-T
• rs13119
• NM_005899.5:c.*628C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005899.5(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 NM_005899.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.506
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005899.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBR1	NM_005899.5	MANE Select	c.*628C>T		3_prime_UTR	Exon 21 of 21	NP_005890.2
	NBR1	NM_031862.4		c.*628C>T		3_prime_UTR	Exon 21 of 21	NP_114068.1
	NBR1	NM_001291572.2		c.*788C>T		3_prime_UTR	Exon 18 of 18	NP_001278501.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBR1	ENST00000590996.6	TSL:1 MANE Select	c.*628C>T		3_prime_UTR	Exon 21 of 21	ENSP00000466667.1
	NBR1	ENST00000341165.10	TSL:1	c.*628C>T		3_prime_UTR	Exon 21 of 21	ENSP00000343479.5

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

African (AFR) AF: 0.174 AC: 1246 AN: 7174

American (AMR) AF: 0.337 AC: 2506 AN: 7434

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 3257 AN: 9232

East Asian (EAS) AF: 0.340 AC: 7770 AN: 22864

South Asian (SAS) AF: 0.505 AC: 1531 AN: 3030

European-Finnish (FIN) AF: 0.394 AC: 8209 AN: 20818

Middle Eastern (MID) AF: 0.379 AC: 489 AN: 1290

European-Non Finnish (NFE) AF: 0.330 AC: 52212 AN: 158006

Other (OTH) AF: 0.333 AC: 5440 AN: 16360

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

African (AFR) AF: 0.180 AC: 7471 AN: 41440

American (AMR) AF: 0.322 AC: 4913 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1215 AN: 3468

East Asian (EAS) AF: 0.369 AC: 1902 AN: 5158

South Asian (SAS) AF: 0.494 AC: 2380 AN: 4822

European-Finnish (FIN) AF: 0.406 AC: 4280 AN: 10554

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22762 AN: 67966

Other (OTH) AF: 0.327 AC: 690 AN: 2110

Alfa AF: 0.314 Hom.: 1619

Bravo AF: 0.286

Asia WGS AF: 0.404 AC: 1405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.3
DANN	Benign	0.74
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism (auto)

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: rs13119; hg19: chr17-41362721;