Variant 20-33083415-C-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.218C>A(p.Pro73Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000057 in 1,613,320 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

BPIFB4
NM_182519.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.265

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=0.038111717).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPIFB4	NM_182519.3 linkuse as main transcript	c.218C>A	p.Pro73Gln	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.218C>A	p.Pro73Gln	missense_variant	5/18	5	NM_182519.3	ENSP00000364632.3	P59827-1
BPIFB4	ENST00000674031.1 linkuse as main transcript	c.584C>A	p.Pro195Gln	missense_variant	2/15			ENSP00000501266.1	A0A669KBJ0
BPIFB4	ENST00000445356.1 linkuse as main transcript	n.106+1783C>A		intron_variant		2		ENSP00000388423.1	F8WEG9

Frequencies

GnomAD3 genomes

AF:

0.000277

AC:

AN:

151744

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000848

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:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.0000835

AC:

AN:

251384

Hom.:

AF XY:

0.0000883

AC XY:

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000342

AC:

AN:

1461576

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.000277

AC:

AN:

151744

Hom.:

Cov.:

AF XY:

0.000297

AC XY:

AN XY:

74066

show subpopulations

Gnomad4 AFR

AF:

0.000848

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000959

Alfa

AF:

0.0000898

Hom.:

Bravo

AF:

0.000291

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

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

May 07, 2024

The c.218C>A (p.P73Q) alteration is located in exon 3 (coding exon 3) of the BPIFB4 gene. This alteration results from a C to A substitution at nucleotide position 218, causing the proline (P) at amino acid position 73 to be replaced by a glutamine (Q). 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

0.082

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.49

CADD

Benign

8.8

DANN

Benign

0.92

DEOGEN2

Benign

0.0053

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.63

M_CAP

Benign

0.0064

MetaRNN

Benign

0.038

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.90

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.79

REVEL

Benign

0.052

Sift

Uncertain

0.0050

Sift4G

Pathogenic

0.0

Polyphen

0.74

Vest4

0.28

MVP

0.061

MPC

0.077

ClinPred

0.018

GERP RS

1.9

Varity_R

0.065

gMVP

0.33

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