Genetic Variant BNIP5:p.Arg192His (chr6-36330116-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001010903.5(BNIP5):c.575G>A(p.Arg192His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,610,526 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 3 hom. )

Consequence

BNIP5
NM_001010903.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.15

Publications

3 publications found

Variant links:

Genes affected

BNIP5 (HGNC:33769): (BCL2 interacting protein 5)

BNIP5 links:

ENSG00000297259 (HGNC:):

ENSG00000297259 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004160762).

BP6

Variant 6-36330116-C-T is Benign according to our data. Variant chr6-36330116-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2656514.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010903.5. 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
	BNIP5	NM_001010903.5	MANE Select	c.575G>A	p.Arg192His	missense	Exon 2 of 12	NP_001010903.3	P0C671

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BNIP5	ENST00000437635.3	TSL:1 MANE Select	c.575G>A	p.Arg192His	missense	Exon 2 of 12	ENSP00000418983.1	P0C671
BNIP5	ENST00000860604.1		c.575G>A	p.Arg192His	missense	Exon 2 of 12	ENSP00000530663.1
BNIP5	ENST00000860607.1		c.575G>A	p.Arg192His	missense	Exon 2 of 12	ENSP00000530666.1

Frequencies

GnomAD3 genomes

AF:

0.00197

AC:

300

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00418

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.000773

Gnomad SAS

AF:

0.00477

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000867

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00144

AC:

359

AN:

249212

AF XY:

0.00158

show subpopulations

Gnomad AFR exome

AF:

0.00394

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00150

Gnomad EAS exome

AF:

0.000926

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000882

Gnomad OTH exome

AF:

0.000819

GnomAD4 exome

AF:

0.00114

AC:

1662

AN:

1458260

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

928

AN XY:

725582

show subpopulations

African (AFR)

AF:

0.00410

AC:

137

AN:

33428

American (AMR)

AF:

0.000314

AC:

AN:

44616

Ashkenazi Jewish (ASJ)

AF:

0.00111

AC:

AN:

26096

East Asian (EAS)

AF:

0.000378

AC:

AN:

39694

South Asian (SAS)

AF:

0.00537

AC:

463

AN:

86206

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50358

Middle Eastern (MID)

AF:

0.00173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000795

AC:

884

AN:

1111774

Other (OTH)

AF:

0.00182

AC:

110

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

199

298

398

497

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<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

AF:

0.00197

AC:

300

AN:

152266

Hom.:

Cov.:

AF XY:

0.00201

AC XY:

150

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.00416

AC:

173

AN:

41552

American (AMR)

AF:

0.000653

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3472

East Asian (EAS)

AF:

0.000775

AC:

AN:

5162

South Asian (SAS)

AF:

0.00477

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000867

AC:

AN:

68024

Other (OTH)

AF:

0.00189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00120

Hom.:

Bravo

AF:

0.00190

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00409

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.00166

AC:

201

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.012

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.010

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0032

LIST_S2

Benign

0.33

M_CAP

Benign

0.0038

MetaRNN

Benign

0.0042

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.69

PhyloP100

-2.1

PROVEAN

Benign

-0.10

REVEL

Benign

0.0050

Sift

Benign

0.57

Sift4G

Benign

0.55

Polyphen

0.0

Vest4

0.11

MVP

0.014

MPC

0.013

ClinPred

0.00024

GERP RS

-4.9

Varity_R

0.015

gMVP

0.041

Mutation Taster

=100/0

polymorphism

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over