20-33291009-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_033197.3(BPIFB1):c.418A>G(p.Thr140Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00287 in 1,613,926 control chromosomes in the GnomAD database, including 109 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 Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 56 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 53 hom. )

Consequence

BPIFB1
NM_033197.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.246

Publications

5 publications found

Variant links:

Genes affected

BPIFB1 (HGNC:16108): (BPI fold containing family B member 1) The protein encoded by this gene may be involved in the innate immune response to bacterial exposure in the mouth, nasal cavities, and lungs. The encoded protein is secreted and is a member of the BPI/LBP/PLUNC protein superfamily. This gene is found with other members of the superfamily in a cluster on chromosome 20. [provided by RefSeq, Jul 2008]

BPIFB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040444434).

BP6

Variant 20-33291009-A-G is Benign according to our data. Variant chr20-33291009-A-G is described in ClinVar as Benign. ClinVar VariationId is 775647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0146 (2217/152264) while in subpopulation AFR AF = 0.0492 (2044/41552). AF 95% confidence interval is 0.0474. There are 56 homozygotes in GnomAd4. There are 1087 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 56 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BPIFB1	NM_033197.3 link	c.418A>G	p.Thr140Ala	missense_variant	Exon 5 of 16	ENST00000253354.2	NP_149974.2	Q8TDL5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BPIFB1	ENST00000253354.2 link	c.418A>G	p.Thr140Ala	missense_variant	Exon 5 of 16	1	NM_033197.3	ENSP00000253354.1		Q8TDL5-1
BPIFB1	ENST00000423645.5 link	c.418A>G	p.Thr140Ala	missense_variant	Exon 5 of 5	3		ENSP00000390471.1		A2A2R0

Frequencies

GnomAD3 genomes

AF:

0.0145

AC:

2210

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0492

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00759

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.0134

GnomAD2 exomes

AF:

0.00370

AC:

927

AN:

250832

AF XY:

0.00285

show subpopulations

Gnomad AFR exome

AF:

0.0484

Gnomad AMR exome

AF:

0.00220

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000335

Gnomad OTH exome

AF:

0.00311

GnomAD4 exome

AF:

0.00166

AC:

2421

AN:

1461662

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

1060

AN XY:

727146

show subpopulations

African (AFR)

AF:

0.0513

AC:

1719

AN:

33478

American (AMR)

AF:

0.00273

AC:

122

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000220

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53218

Middle Eastern (MID)

AF:

0.00676

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000237

AC:

264

AN:

1111998

Other (OTH)

AF:

0.00427

AC:

258

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

135

269

404

538

673

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<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:

0.0146

AC:

2217

AN:

152264

Hom.:

Cov.:

AF XY:

0.0146

AC XY:

1087

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0492

AC:

2044

AN:

41552

American (AMR)

AF:

0.00758

AC:

116

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.000208

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000382

AC:

AN:

68014

Other (OTH)

AF:

0.0132

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

117

234

351

468

585

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.00525

Hom.:

Bravo

AF:

0.0169

ESP6500AA

AF:

0.0374

AC:

165

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00434

AC:

527

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 26, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.16

(source)

DANN

Benign

0.41

DEOGEN2

Benign

0.0054

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.35

T;T

MetaRNN

Benign

0.0040

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

.;N

PhyloP100

-0.25

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.10

N;N

REVEL

Benign

0.049

Sift

Uncertain

0.015

D;T

Sift4G

Uncertain

0.016

D;D

Polyphen

0.0

.;B

Vest4

0.21

MVP

0.014

MPC

0.17

ClinPred

0.0068

GERP RS

-4.7

Varity_R

0.027

gMVP

0.095

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over