Variant 20-33291009-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 56 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPIFB1	NM_033197.3 linkuse as main transcript	c.418A>G	p.Thr140Ala	missense_variant	5/16	ENST00000253354.2	NP_149974.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BPIFB1	ENST00000253354.2 linkuse as main transcript	c.418A>G	p.Thr140Ala	missense_variant	5/16	1	NM_033197.3	ENSP00000253354	P1	Q8TDL5-1
BPIFB1	ENST00000423645.5 linkuse as main transcript	c.418A>G	p.Thr140Ala	missense_variant	5/5	3		ENSP00000390471

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

GnomAD3 exomes

AF:

0.00370

AC:

927

AN:

250832

Hom.:

AF XY:

0.00285

AC XY:

386

AN XY:

135652

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 SAS exome

AF:

0.000327

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

Gnomad4 AFR exome

AF:

0.0513

Gnomad4 AMR exome

AF:

0.00273

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000237

Gnomad4 OTH exome

AF:

0.00427

GnomAD4 genome

AF:

0.0146

AC:

2217

AN:

152264

Hom.:

Cov.:

AF XY:

0.0146

AC XY:

1087

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0492

Gnomad4 AMR

AF:

0.00758

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.00171

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 26, 2018	- -

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

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

MutationTaster

Benign

1.0

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over