Variant chr20-33083375-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_182519.3(BPIFB4):c.178G>A(p.Asp60Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000157 in 1,612,896 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 29)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

BPIFB4
NM_182519.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.21

Variant links:

Genes affected

BPIFB4 (HGNC:16179): (BPI fold containing family B member 4) Predicted to enable lipid binding activity. Predicted to be located in cytoplasm and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

BPIFB4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06105739).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPIFB4	NM_182519.3 linkuse as main transcript	c.178G>A	p.Asp60Asn	missense_variant	5/18	ENST00000375483.4	NP_872325.2	P59827-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BPIFB4	ENST00000375483.4 linkuse as main transcript	c.178G>A	p.Asp60Asn	missense_variant	5/18	5	NM_182519.3	ENSP00000364632.3	P59827-1
BPIFB4	ENST00000674031.1 linkuse as main transcript	c.544G>A	p.Asp182Asn	missense_variant	2/15			ENSP00000501266.1	A0A669KBJ0
BPIFB4	ENST00000445356.1 linkuse as main transcript	n.106+1743G>A		intron_variant		2		ENSP00000388423.1	F8WEG9

Frequencies

GnomAD3 genomes

AF:

0.000178

AC:

AN:

151812

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000727

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000183

AC:

AN:

250834

Hom.:

AF XY:

0.000170

AC XY:

AN XY:

135536

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000326

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000155

AC:

226

AN:

1461084

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

110

AN XY:

726792

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000184

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000178

AC:

AN:

151812

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74126

show subpopulations

Gnomad4 AFR

AF:

0.0000727

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000206

Hom.:

Bravo

AF:

0.000185

ExAC

AF:

0.000239

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000533

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2021

The c.178G>A (p.D60N) alteration is located in exon 3 (coding exon 3) of the BPIFB4 gene. This alteration results from a G to A substitution at nucleotide position 178, causing the aspartic acid (D) at amino acid position 60 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.71

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0024

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.39

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.65

M_CAP

Benign

0.0046

MetaRNN

Benign

0.061

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.59

PROVEAN

Benign

0.0

REVEL

Benign

0.15

Sift

Uncertain

0.018

Sift4G

Benign

0.15

Polyphen

0.0

Vest4

0.23

MVP

0.014

MPC

0.055

ClinPred

0.069

GERP RS

2.9

Varity_R

0.084

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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