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GeneBe

17-43190720-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_005899.5(NBR1):c.807G>A(p.Pro269=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00388 in 1,613,720 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0039 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0039 ( 13 hom. )

Consequence

NBR1
NM_005899.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.11
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-43190720-G-A is Benign according to our data. Variant chr17-43190720-G-A is described in ClinVar as [Benign]. Clinvar id is 774233.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.11 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome at 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NBR1NM_005899.5 linkuse as main transcriptc.807G>A p.Pro269= synonymous_variant 9/21 ENST00000590996.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NBR1ENST00000590996.6 linkuse as main transcriptc.807G>A p.Pro269= synonymous_variant 9/211 NM_005899.5 P1Q14596-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00393
AC:
598
AN:
152180
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000965
Gnomad AMI
AF:
0.00219
Gnomad AMR
AF:
0.00491
Gnomad ASJ
AF:
0.0159
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00377
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00551
Gnomad OTH
AF:
0.00431
GnomAD3 exomes
AF:
0.00391
AC:
972
AN:
248764
Hom.:
5
AF XY:
0.00380
AC XY:
513
AN XY:
134960
show subpopulations
Gnomad AFR exome
AF:
0.00142
Gnomad AMR exome
AF:
0.00363
Gnomad ASJ exome
AF:
0.0150
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00404
Gnomad NFE exome
AF:
0.00492
Gnomad OTH exome
AF:
0.00481
GnomAD4 exome
AF:
0.00388
AC:
5666
AN:
1461422
Hom.:
13
Cov.:
30
AF XY:
0.00382
AC XY:
2779
AN XY:
726970
show subpopulations
Gnomad4 AFR exome
AF:
0.00105
Gnomad4 AMR exome
AF:
0.00349
Gnomad4 ASJ exome
AF:
0.0149
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000197
Gnomad4 FIN exome
AF:
0.00401
Gnomad4 NFE exome
AF:
0.00414
Gnomad4 OTH exome
AF:
0.00368
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00393
AC:
598
AN:
152298
Hom.:
1
Cov.:
32
AF XY:
0.00408
AC XY:
304
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.000962
Gnomad4 AMR
AF:
0.00490
Gnomad4 ASJ
AF:
0.0159
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00377
Gnomad4 NFE
AF:
0.00551
Gnomad4 OTH
AF:
0.00426
Alfa
AF:
0.00521
Hom.:
0
Bravo
AF:
0.00373
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00545
EpiControl
AF:
0.00504

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 12, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
Cadd
Benign
1.5
Dann
Benign
0.54
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs200554551; hg19: chr17-41342737; API