Genetic Variant BMF:p.Glu2Gln (chr15-40106083-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001003940.2(BMF):c.4G>C(p.Glu2Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000193 in 1,598,040 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 3 hom. )

Consequence

BMF
NM_001003940.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.40

Publications

1 publications found

Variant links:

Genes affected

BMF (HGNC:24132): (Bcl2 modifying factor) The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein contains a single BCL2 homology domain 3 (BH3), and has been shown to bind BCL2 proteins and function as an apoptotic activator. This protein is found to be sequestered to myosin V motors by its association with dynein light chain 2, which may be important for sensing intracellular damage and triggering apoptosis. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

BMF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09901446).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003940.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BMF	NM_001003940.2	MANE Select	c.4G>C	p.Glu2Gln	missense	Exon 3 of 5	NP_001003940.1	Q96LC9-1
BMF	NM_001398495.1		c.4G>C	p.Glu2Gln	missense	Exon 3 of 5	NP_001385424.1	Q96LC9-1
BMF	NM_001398496.1		c.4G>C	p.Glu2Gln	missense	Exon 2 of 4	NP_001385425.1	Q96LC9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BMF	ENST00000354670.9	TSL:1 MANE Select	c.4G>C	p.Glu2Gln	missense	Exon 3 of 5	ENSP00000346697.4	Q96LC9-1
BMF	ENST00000397573.5	TSL:1	c.4G>C	p.Glu2Gln	missense	Exon 2 of 4	ENSP00000380703.1	Q96LC9-1
BMF	ENST00000561282.5	TSL:1	c.4G>C	p.Glu2Gln	missense	Exon 2 of 4	ENSP00000453522.1	Q96LC9-1

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000264

AC:

AN:

238346

AF XY:

0.000358

show subpopulations

Gnomad AFR exome

AF:

0.0000620

Gnomad AMR exome

AF:

0.000268

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000548

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000212

Gnomad OTH exome

AF:

0.000691

GnomAD4 exome

AF:

0.000194

AC:

281

AN:

1445744

Hom.:

Cov.:

AF XY:

0.000236

AC XY:

169

AN XY:

717340

show subpopulations

African (AFR)

AF:

0.0000601

AC:

AN:

33292

American (AMR)

AF:

0.000342

AC:

AN:

43902

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25180

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39472

South Asian (SAS)

AF:

0.000663

AC:

AN:

84424

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50812

Middle Eastern (MID)

AF:

0.00246

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.000149

AC:

164

AN:

1103198

Other (OTH)

AF:

0.000485

AC:

AN:

59766

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

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

AF:

0.000184

AC:

AN:

152296

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41564

American (AMR)

AF:

0.000719

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

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:

0.000260

Hom.:

Bravo

AF:

0.000212

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000272

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Benign

0.12

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.46

M_CAP

Benign

0.0058

MetaRNN

Benign

0.099

MetaSVM

Benign

-0.70

MutationAssessor

Benign

0.90

PhyloP100

4.4

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.4

REVEL

Benign

0.16

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.36

MVP

0.45

MPC

0.26

ClinPred

0.12

GERP RS

5.1

PromoterAI

0.011

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.34

gMVP

0.21

Mutation Taster

=82/18

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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