15-59680251-C-G

Position:

• chr15-59680251-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004330.4(BNIP2):​c.108G>C​(p.Glu36Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BNIP2 NM_004330.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.187

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056933165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BNIP2	NM_004330.4	c.108G>C	p.Glu36Asp	missense_variant	3/10	ENST00000607373.6	NP_004321.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BNIP2	ENST00000607373.6	c.108G>C	p.Glu36Asp	missense_variant	3/10	1	NM_004330.4	ENSP00000475320.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2024

The c.471G>C (p.E157D) alteration is located in exon 3 (coding exon 3) of the BNIP2 gene. This alteration results from a G to C substitution at nucleotide position 471, causing the glutamic acid (E) at amino acid position 157 to be replaced by an aspartic acid (D). 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	Benign	0.069
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T;T;T;.
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.59	.;T;T;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.057	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	.;.;N;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.39	N;.;.;N
REVEL	Benign	0.042
Sift	Benign	0.23	T;.;.;T
Sift4G	Benign	0.33	T;T;T;T
Polyphen		0.0	.;.;B;B
Vest4		0.11
MutPred		0.16		.;.;Gain of phosphorylation at T33 (P = 0.1935);.;
MVP		0.53
MPC		0.018
ClinPred		0.25	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.062
gMVP		0.027

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.

Other links and lift over

hg19: chr15-59972450;