Genetic Variant NM_004330.4:c.769C>G (chr15-59669301-G-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_004330.4(BNIP2):c.769C>G(p.Leu257Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,558,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

BNIP2
NM_004330.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.70

Publications

0 publications found

Variant links:

Genes affected

BNIP2 (HGNC:1083): (BCL2 interacting protein 2) This gene is a member of the BCL2/adenovirus E1B 19 kd-interacting protein (BNIP) family. It interacts with the E1B 19 kDa protein, which protects cells from virally-induced cell death. The encoded protein also interacts with E1B 19 kDa-like sequences of BCL2, another apoptotic protector. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

BNIP2 links:

ENSG00000227161 (HGNC:):

ENSG00000227161 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.788

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004330.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BNIP2	NM_004330.4	MANE Select	c.769C>G	p.Leu257Val	missense	Exon 8 of 10	NP_004321.3	Q12982-1
BNIP2	NM_001320674.2		c.769C>G	p.Leu257Val	missense	Exon 8 of 11	NP_001307603.2	H7C096
BNIP2	NM_001320675.4		c.769C>G	p.Leu257Val	missense	Exon 8 of 10	NP_001307604.2	Q12982-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BNIP2	ENST00000607373.6	TSL:1 MANE Select	c.769C>G	p.Leu257Val	missense	Exon 8 of 10	ENSP00000475320.1	Q12982-1
BNIP2	ENST00000439052.6	TSL:2	c.769C>G	p.Leu257Val	missense	Exon 8 of 11	ENSP00000393644.2	H7C096
BNIP2	ENST00000897502.1		c.769C>G	p.Leu257Val	missense	Exon 8 of 11	ENSP00000567561.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151894

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000464

AC:

AN:

215452

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000974

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000107

AC:

AN:

1406658

Hom.:

Cov.:

AF XY:

0.0000115

AC XY:

AN XY:

698460

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30590

American (AMR)

AF:

0.00

AC:

AN:

32814

Ashkenazi Jewish (ASJ)

AF:

0.0000405

AC:

AN:

24712

East Asian (EAS)

AF:

0.00

AC:

AN:

38204

South Asian (SAS)

AF:

0.00

AC:

AN:

73394

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52070

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5552

European-Non Finnish (NFE)

AF:

0.0000128

AC:

AN:

1091448

Other (OTH)

AF:

0.00

AC:

AN:

57874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.418

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151894

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74176

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41354

American (AMR)

AF:

0.00

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10496

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68000

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.17

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.087

Eigen

Benign

0.069

Eigen_PC

Benign

0.10

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.19

MetaRNN

Pathogenic

0.79

MetaSVM

Uncertain

-0.094

MutationAssessor

Benign

1.4

PhyloP100

4.7

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.0

REVEL

Pathogenic

0.74

Sift

Benign

0.11

Sift4G

Benign

0.082

Polyphen

0.72

Vest4

0.65

MVP

0.79

MPC

0.15

ClinPred

0.96

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.20

gMVP

0.75

Mutation Taster

=55/45

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over