Genetic Variant BFAR:p.Ala90Val (chr16-14648393-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016561.3(BFAR):c.269C>T(p.Ala90Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000186 in 1,610,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

BFAR
NM_016561.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.82

Publications

0 publications found

Variant links:

Genes affected

BFAR (HGNC:17613): (bifunctional apoptosis regulator) Enables caspase binding activity; protein-macromolecule adaptor activity; and ubiquitin protein ligase activity. Involved in negative regulation of IRE1-mediated unfolded protein response; proteasome-mediated ubiquitin-dependent protein catabolic process; and protein ubiquitination. Acts upstream of or within negative regulation of apoptotic process. Located in endoplasmic reticulum and membrane. [provided by Alliance of Genome Resources, Apr 2022]

BFAR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05789438).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016561.3. 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
	BFAR	NM_016561.3	MANE Select	c.269C>T	p.Ala90Val	missense	Exon 3 of 8	NP_057645.1	Q9NZS9-1
	BFAR	NM_001330500.2		c.263+3784C>T		intron	N/A	NP_001317429.1	H3BMP2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BFAR	ENST00000261658.7	TSL:1 MANE Select	c.269C>T	p.Ala90Val	missense	Exon 3 of 8	ENSP00000261658.2	Q9NZS9-1
BFAR	ENST00000911310.1		c.269C>T	p.Ala90Val	missense	Exon 3 of 9	ENSP00000581369.1
BFAR	ENST00000901102.1		c.269C>T	p.Ala90Val	missense	Exon 4 of 9	ENSP00000571161.1

Frequencies

GnomAD3 genomes

AF:

0.0000461

AC:

AN:

151832

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000319

AC:

AN:

250898

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.000248

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1458214

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

725684

show subpopulations

African (AFR)

AF:

0.000239

AC:

AN:

33410

American (AMR)

AF:

0.000134

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26102

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86164

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53134

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00000541

AC:

AN:

1108974

Other (OTH)

AF:

0.0000332

AC:

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

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:

0.0000526

AC:

AN:

151950

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.000193

AC:

AN:

41438

American (AMR)

AF:

0.00

AC:

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10524

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67970

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

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:

0.00

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000247

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

Benign

0.15

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.0036

Eigen

Benign

-0.20

Eigen_PC

Benign

0.073

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0044

MetaRNN

Benign

0.058

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

3.8

PrimateAI

Uncertain

0.55

PROVEAN

Benign

0.23

REVEL

Benign

0.087

Sift

Benign

0.61

Sift4G

Benign

0.64

Polyphen

0.0060

Vest4

0.15

MVP

0.54

MPC

0.11

ClinPred

0.042

GERP RS

6.1

PromoterAI

0.033

Neutral

(source)

Varity_R

0.040

gMVP

0.62

Mutation Taster

=79/21

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