Genetic Variant BNIP1:p.Leu62Phe (chr5-173151572-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_013979.3(BNIP1):c.184C>T(p.Leu62Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000092 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BNIP1
NM_013979.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.884

Variant links:

Genes affected

BNIP1 (HGNC:1082): (BCL2 interacting protein 1) 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. In addition, this protein is involved in vesicle transport into the endoplasmic reticulum. Alternative splicing of this gene results in four protein products with identical N- and C-termini. [provided by RefSeq, Mar 2011]

BNIP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.059454173).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BNIP1	NM_001205.3 link	c.178-2750C>T		intron_variant	Intron 2 of 5	ENST00000351486.10	NP_001196.2	Q12981-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BNIP1	ENST00000231668.13 link	c.184C>T	p.Leu62Phe	missense_variant	Exon 3 of 7	1		ENSP00000231668.9	Q12981-1
BNIP1	ENST00000352523.10 link	c.184C>T	p.Leu62Phe	missense_variant	Exon 3 of 6	1		ENSP00000239214.8	Q12981-3
BNIP1	ENST00000351486.10 link	c.178-2750C>T		intron_variant	Intron 2 of 5	1	NM_001205.3	ENSP00000239215.7	Q12981-4
BNIP1	ENST00000393770.4 link	c.178-2750C>T		intron_variant	Intron 2 of 4	1		ENSP00000377365.4	Q12981-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

144676

Hom.:

Cov.:

FAILED QC

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000892

AC:

AN:

224254

Hom.:

AF XY:

0.00

AC XY:

AN XY:

121600

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 SAS exome

AF:

0.0000393

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000956

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000922

AC:

AN:

1409944

Hom.:

Cov.:

AF XY:

0.00000570

AC XY:

AN XY:

701426

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000135

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000377

Gnomad4 FIN exome

AF:

0.0000204

Gnomad4 NFE exome

AF:

0.00000276

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

144676

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

69974

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 30, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.184C>T (p.L62F) alteration is located in exon 3 (coding exon 3) of the BNIP1 gene. This alteration results from a C to T substitution at nucleotide position 184, causing the leucine (L) at amino acid position 62 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.9

DANN

Uncertain

0.98

Eigen

Benign

-0.93

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0098

LIST_S2

Benign

0.35

T;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.059

T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.24

N;N

REVEL

Benign

0.034

Sift

Benign

0.18

T;D

Sift4G

Benign

0.32

T;T

Polyphen

0.0020

B;B

Vest4

0.067

MutPred

0.23

Loss of helix (P = 0.079);Loss of helix (P = 0.079);

MVP

0.22

MPC

0.34

ClinPred

0.024

GERP RS

0.24

gMVP

0.080

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