Genetic Variant BNIP2:p.Arg238Gln (chr15-59669357-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004330.4(BNIP2):c.713G>A(p.Arg238Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000213 in 1,358,750 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

BNIP2
NM_004330.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.16

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.713G>A	p.Arg238Gln	missense	Exon 8 of 10	NP_004321.3	Q12982-1
BNIP2	NM_001320674.2		c.713G>A	p.Arg238Gln	missense	Exon 8 of 11	NP_001307603.2	H7C096
BNIP2	NM_001320675.4		c.713G>A	p.Arg238Gln	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.713G>A	p.Arg238Gln	missense	Exon 8 of 10	ENSP00000475320.1	Q12982-1
BNIP2	ENST00000439052.6	TSL:2	c.713G>A	p.Arg238Gln	missense	Exon 8 of 11	ENSP00000393644.2	H7C096
BNIP2	ENST00000897502.1		c.713G>A	p.Arg238Gln	missense	Exon 8 of 11	ENSP00000567561.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000207

AC:

AN:

193038

AF XY:

0.0000282

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000765

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000211

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000213

AC:

AN:

1358750

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

674512

show subpopulations

African (AFR)

AF:

0.0000349

AC:

AN:

28686

American (AMR)

AF:

0.00

AC:

AN:

28588

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23024

East Asian (EAS)

AF:

0.0000273

AC:

AN:

36594

South Asian (SAS)

AF:

0.0000301

AC:

AN:

66442

European-Finnish (FIN)

AF:

0.0000399

AC:

AN:

50088

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5348

European-Non Finnish (NFE)

AF:

0.0000207

AC:

AN:

1064380

Other (OTH)

AF:

0.0000180

AC:

AN:

55600

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000330

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

Pathogenic

0.95

BayesDel_addAF

Benign

-0.028

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.27

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.99

M_CAP

Uncertain

0.16

MetaRNN

Uncertain

0.66

MetaSVM

Uncertain

0.69

MutationAssessor

Pathogenic

2.9

PhyloP100

3.2

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.9

REVEL

Pathogenic

0.79

Sift

Uncertain

0.023

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.69

MutPred

0.61

Loss of MoRF binding (P = 0.0591)

MVP

0.95

MPC

0.16

ClinPred

0.99

GERP RS

4.9

Varity_R

0.41

gMVP

0.74

Mutation Taster

=74/26

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over