Variant 17-43190720-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The ENST00000590996.6(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
ENST00000590996.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

NBR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.11 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NBR1	NM_005899.5 linkuse as main transcript	c.807G>A	p.Pro269=	synonymous_variant	9/21	ENST00000590996.6	NP_005890.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NBR1	ENST00000590996.6 linkuse as main transcript	c.807G>A	p.Pro269=	synonymous_variant	9/21	1	NM_005899.5	ENSP00000466667	P1	Q14596-1

Frequencies

GnomAD3 genomes

AF:

0.00393

AC:

598

AN:

152180

Hom.:

Cov.:

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.:

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.:

Cov.:

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

AF:

0.00393

AC:

598

AN:

152298

Hom.:

Cov.:

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.:

Bravo

AF:

0.00373

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00545

EpiControl

AF:

0.00504

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over