15-59680251-C-G

Variant names:

• chr15-59680251-C-G
• NM_004330.4:c.108G>C

Variant summary

Our verdict is Likely benign. The variant received -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. 15/22 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
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BNIP2	NM_004330.4	MANE Select	c.108G>C	p.Glu36Asp	missense	Exon 3 of 10	NP_004321.3	Q12982-1
	BNIP2	NM_001320674.2		c.108G>C	p.Glu36Asp	missense	Exon 3 of 11	NP_001307603.2	H7C096
	BNIP2	NM_001320675.4		c.108G>C	p.Glu36Asp	missense	Exon 3 of 10	NP_001307604.2	Q12982-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BNIP2	ENST00000607373.6	TSL:1 MANE Select	c.108G>C	p.Glu36Asp	missense	Exon 3 of 10	ENSP00000475320.1	Q12982-1
	BNIP2	ENST00000439052.6	TSL:2	c.108G>C	p.Glu36Asp	missense	Exon 3 of 11	ENSP00000393644.2	H7C096
	BNIP2	ENST00000897502.1		c.108G>C	p.Glu36Asp	missense	Exon 3 of 11	ENSP00000567561.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.19
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.042
Sift	Benign	0.23	T
Sift4G	Benign	0.33	T
Polyphen		0.0	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
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

hg19: chr15-59972450;