dbSNP rs17304572: BPIFA2:p.Lys113Glu (chr20-33174113-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_080574.4(BPIFA2):c.337A>G(p.Lys113Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00849 in 1,614,144 control chromosomes in the GnomAD database, including 198 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0083 ( 18 hom., cov: 32)

Exomes 𝑓: 0.0085 ( 180 hom. )

Consequence

BPIFA2
NM_080574.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.417

Publications

9 publications found

Variant links:

Genes affected

BPIFA2 (HGNC:16203): (BPI fold containing family A member 2) This gene encodes a member of the palate, lung and nasal epithelium clone (Plunc) family of proteins. Members of this family have been proposed to play a role in the local antibacterial response in nose, mouth and upper respiratory pathways. The encoded soluble salivary protein binds bacterial lipopolysaccharide (LPS) and inhibits bacterial growth. This gene is present in a gene cluster on chromosome 20. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

BPIFA2 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 (MetaRNN=0.0026183426).

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BPIFA2	NM_080574.4 link	c.337A>G	p.Lys113Glu	missense_variant	Exon 4 of 9	ENST00000354932.6	NP_542141.1	Q96DR5A8K739
BPIFA2	NM_001319164.2 link	c.337A>G	p.Lys113Glu	missense_variant	Exon 4 of 9		NP_001306093.1	Q96DR5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BPIFA2	ENST00000354932.6 link	c.337A>G	p.Lys113Glu	missense_variant	Exon 4 of 9	1	NM_080574.4	ENSP00000347012.5		Q96DR5
BPIFA2	ENST00000253362.6 link	c.337A>G	p.Lys113Glu	missense_variant	Exon 4 of 9	1		ENSP00000253362.2		Q96DR5

Frequencies

GnomAD3 genomes

AF:

0.00821

AC:

1250

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00251

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0403

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00707

Gnomad OTH

AF:

0.00861

GnomAD2 exomes

AF:

0.0146

AC:

3680

AN:

251474

AF XY:

0.0119

show subpopulations

Gnomad AFR exome

AF:

0.00215

Gnomad AMR exome

AF:

0.0754

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00249

Gnomad NFE exome

AF:

0.00763

Gnomad OTH exome

AF:

0.0112

GnomAD4 exome

AF:

0.00851

AC:

12439

AN:

1461846

Hom.:

180

Cov.:

AF XY:

0.00786

AC XY:

5719

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.00140

AC:

AN:

33476

American (AMR)

AF:

0.0732

AC:

3272

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000574

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00147

AC:

127

AN:

86258

European-Finnish (FIN)

AF:

0.00324

AC:

173

AN:

53418

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00754

AC:

8379

AN:

1111974

Other (OTH)

AF:

0.00694

AC:

419

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

629

1258

1886

2515

3144

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

360

720

1080

1440

1800

<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:

0.00827

AC:

1260

AN:

152298

Hom.:

Cov.:

AF XY:

0.00823

AC XY:

613

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00250

AC:

104

AN:

41562

American (AMR)

AF:

0.0409

AC:

625

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00145

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00217

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00707

AC:

481

AN:

68022

Other (OTH)

AF:

0.00852

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

122

183

244

305

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00831

Hom.:

Bravo

AF:

0.0119

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00778

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00756

AC:

ExAC

AF:

0.0129

AC:

1562

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.00480

EpiControl

AF:

0.00622

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.00071

T;T

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.34

.;T

MetaRNN

Benign

0.0026

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L

PhyloP100

0.42

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.71

N;N

REVEL

Benign

0.030

Sift

Benign

0.072

T;T

Sift4G

Benign

0.096

T;T

Polyphen

0.76

P;P

Vest4

0.040

MPC

0.46

ClinPred

0.023

GERP RS

0.54

Varity_R

0.072

gMVP

0.12

Mutation Taster

=97/3

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over