Variant chr20-33083531-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_182519.3(BPIFB4):c.334G>A(p.Glu112Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,613,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

BPIFB4
NM_182519.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.82

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08332926).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BPIFB4	NM_182519.3 linkuse as main transcript	c.334G>A	p.Glu112Lys	missense_variant	5/18	ENST00000375483.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BPIFB4	ENST00000375483.4 linkuse as main transcript	c.334G>A	p.Glu112Lys	missense_variant	5/18	5	NM_182519.3	P1	P59827-1
BPIFB4	ENST00000674031.1 linkuse as main transcript	c.700G>A	p.Glu234Lys	missense_variant	2/15
BPIFB4	ENST00000445356.1 linkuse as main transcript	c.106+1899G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000278

AC:

AN:

251410

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000150

AC:

AN:

1461832

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000302

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152060

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ExAC

AF:

0.0000330

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

Jun 29, 2023

The c.334G>A (p.E112K) 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 334, causing the glutamic acid (E) at amino acid position 112 to be replaced by a lysine (K). 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

0.10

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0020

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.74

M_CAP

Benign

0.0063

MetaRNN

Benign

0.083

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.23

REVEL

Benign

0.11

Sift

Uncertain

0.0050

Sift4G

Benign

0.096

Polyphen

0.17

Vest4

0.23

MutPred

0.43

Gain of MoRF binding (P = 0.0025);

MVP

0.014

MPC

0.067

ClinPred

0.13

GERP RS

3.3

Varity_R

0.096

gMVP

0.24

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