rs8070085

chr17-43189967-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.695+165A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 636,402 control chromosomes in the GnomAD database, including 39,248 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 0.32 (8044 hom., cov: 32)
  • Exomes 𝑓: 0.35 (31204 hom.)
• Consequence: NBR1 NM_005899.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBR1	NM_005899.5	c.695+165A>G		intron_variant		ENST00000590996.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBR1	ENST00000590996.6	c.695+165A>G		intron_variant		1	NM_005899.5	P1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48315 AN: 151970 Hom.: 8038 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.336

GnomAD4 exome AF: 0.354 AC: 171492 AN: 484314 Hom.: 31204 Cov.: 6 AF XY: 0.362 AC XY: 92715 AN XY: 255834

Gnomad4 AFR exome AF: 0.233

Gnomad4 AMR exome AF: 0.331

Gnomad4 ASJ exome AF: 0.363

Gnomad4 EAS exome AF: 0.351

Gnomad4 SAS exome AF: 0.504

Gnomad4 FIN exome AF: 0.393

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.344

GnomAD4 genome AF: 0.318 AC: 48351 AN: 152088 Hom.: 8044 Cov.: 32 AF XY: 0.324 AC XY: 24104 AN XY: 74360

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.360

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.406

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.340

Alfa AF: 0.321 Hom.: 1935

Bravo AF: 0.303

Asia WGS AF: 0.418 AC: 1454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.6
Dann	Benign	0.48

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: rs8070085; hg19: chr17-41341984; COSMIC: COSV57831125;