rs8070085

Variant names:

• chr17-43189967-A-G
• rs8070085
• NM_005899.5:c.695+165A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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=-0.9).
• 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 rank	MANE	Protein	UniProt
NBR1	NM_005899.5	c.695+165A>G		intron_variant	Intron 8 of 20	ENST00000590996.6	NP_005890.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBR1	ENST00000590996.6	c.695+165A>G		intron_variant	Intron 8 of 20	1	NM_005899.5	ENSP00000466667.1

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

African (AFR) AF: 0.233 AC: 3131 AN: 13422

American (AMR) AF: 0.331 AC: 6644 AN: 20092

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 5074 AN: 13990

East Asian (EAS) AF: 0.351 AC: 11288 AN: 32170

South Asian (SAS) AF: 0.504 AC: 24526 AN: 48634

European-Finnish (FIN) AF: 0.393 AC: 12231 AN: 31154

Middle Eastern (MID) AF: 0.384 AC: 776 AN: 2022

European-Non Finnish (NFE) AF: 0.333 AC: 98428 AN: 295550

Other (OTH) AF: 0.344 AC: 9394 AN: 27280

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

African (AFR) AF: 0.230 AC: 9542 AN: 41482

American (AMR) AF: 0.332 AC: 5068 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1247 AN: 3466

East Asian (EAS) AF: 0.369 AC: 1913 AN: 5180

South Asian (SAS) AF: 0.495 AC: 2389 AN: 4826

European-Finnish (FIN) AF: 0.406 AC: 4290 AN: 10572

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22822 AN: 67976

Other (OTH) AF: 0.340 AC: 717 AN: 2110

Alfa AF: 0.320 Hom.: 2074

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
PhyloP100		-0.030
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: rs8070085; hg19: chr17-41341984; COSMIC: COSV57831125;