Variant chr5-173163850-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001205.3(BNIP1):c.616T>C(p.Phe206Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,766 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: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

BNIP1
NM_001205.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.811

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BNIP1	NM_001205.3 linkuse as main transcript	c.616T>C	p.Phe206Leu	missense_variant	6/6	ENST00000351486.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BNIP1	ENST00000351486.10 linkuse as main transcript	c.616T>C	p.Phe206Leu	missense_variant	6/6	1	NM_001205.3	P1	Q12981-4
BNIP1	ENST00000231668.13 linkuse as main transcript	c.745T>C	p.Phe249Leu	missense_variant	7/7	1			Q12981-1
BNIP1	ENST00000352523.10 linkuse as main transcript	c.643T>C	p.Phe215Leu	missense_variant	6/6	1			Q12981-3
BNIP1	ENST00000393770.4 linkuse as main transcript	c.514T>C	p.Phe172Leu	missense_variant	5/5	1			Q12981-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461766

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2022

The c.745T>C (p.F249L) alteration is located in exon 7 (coding exon 7) of the BNIP1 gene. This alteration results from a T to C substitution at nucleotide position 745, causing the phenylalanine (F) at amino acid position 249 to be replaced by a leucine (L). 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

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

.;T;.;.

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

D;D;D;D

M_CAP

Benign

0.022

MetaRNN

Pathogenic

0.81

D;D;D;D

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.2

.;M;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-3.7

D;D;D;D

REVEL

Benign

0.28

Sift

Uncertain

0.023

D;D;D;D

Sift4G

Uncertain

0.018

D;T;T;T

Polyphen

0.94

P;P;P;D

Vest4

0.70

MutPred

0.74

.;Gain of catalytic residue at F206 (P = 0.0461);.;.;

MVP

0.62

MPC

0.89

ClinPred

0.98

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.38

gMVP

0.75

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over