Genetic Variant BNIP2:c.*4695T>C (chr15-59659374-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004330.4(BNIP2):c.*4695T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 152,106 control chromosomes in the GnomAD database, including 24,725 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.56 ( 24725 hom., cov: 33)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

BNIP2
NM_004330.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.958

Publications

11 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

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	Effect	Exon Rank	Protein
BNIP2	NM_004330.4	MANE Select	c.*4695T>C	3_prime_UTR	Exon 10 of 10	NP_004321.3
BNIP2	NM_001320674.2		c.*4695T>C	3_prime_UTR	Exon 11 of 11	NP_001307603.2
BNIP2	NM_001320675.4		c.*4695T>C	3_prime_UTR	Exon 10 of 10	NP_001307604.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BNIP2	ENST00000607373.6	TSL:1 MANE Select	c.*4695T>C		3_prime_UTR	Exon 10 of 10	ENSP00000475320.1
	ENSG00000227161	ENST00000441746.1	TSL:3	n.68+12861T>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.562

AC:

85485

AN:

151984

Hom.:

24713

Cov.:

show subpopulations

Gnomad AFR

AF:

0.543

Gnomad AMI

AF:

0.666

Gnomad AMR

AF:

0.563

Gnomad ASJ

AF:

0.544

Gnomad EAS

AF:

0.173

Gnomad SAS

AF:

0.389

Gnomad FIN

AF:

0.530

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.620

Gnomad OTH

AF:

0.576

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.562

AC:

85537

AN:

152102

Hom.:

24725

Cov.:

AF XY:

0.553

AC XY:

41116

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.543

AC:

22515

AN:

41464

American (AMR)

AF:

0.563

AC:

8612

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.544

AC:

1889

AN:

3470

East Asian (EAS)

AF:

0.173

AC:

895

AN:

5182

South Asian (SAS)

AF:

0.388

AC:

1873

AN:

4826

European-Finnish (FIN)

AF:

0.530

AC:

5607

AN:

10574

Middle Eastern (MID)

AF:

0.647

AC:

189

AN:

292

European-Non Finnish (NFE)

AF:

0.620

AC:

42139

AN:

67984

Other (OTH)

AF:

0.574

AC:

1211

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1904

3808

5712

7616

9520

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

712

1424

2136

2848

3560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.596

Hom.:

14044

Bravo

AF:

0.565

Asia WGS

AF:

0.318

AC:

1107

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.66

(source)

DANN

Benign

0.66

PhyloP100

-0.96

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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