Variant 20-33064701-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001376932.3(BPIFB3):c.768C>A(p.Asp256Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,614,056 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00093 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0015 ( 3 hom. )

Consequence

BPIFB3
NM_001376932.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.394

Variant links:

Genes affected

BPIFB3 (HGNC:16178): (BPI fold containing family B member 3) Predicted to enable lipid binding activity. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

BPIFB3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08296627).

BS2

High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BPIFB3	NM_001376932.3 linkuse as main transcript	c.768C>A	p.Asp256Glu	missense_variant	9/16	ENST00000375494.4
BPIFB3	NM_182658.5 linkuse as main transcript	c.768C>A	p.Asp256Glu	missense_variant	8/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BPIFB3	ENST00000375494.4 linkuse as main transcript	c.768C>A	p.Asp256Glu	missense_variant	9/16	1	NM_001376932.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000927

AC:

141

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00184

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000732

AC:

184

AN:

251220

Hom.:

AF XY:

0.000707

AC XY:

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000509

Gnomad NFE exome

AF:

0.00138

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.00145

AC:

2124

AN:

1461776

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

1010

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000318

Gnomad4 NFE exome

AF:

0.00180

Gnomad4 OTH exome

AF:

0.00139

GnomAD4 genome

AF:

0.000926

AC:

141

AN:

152280

Hom.:

Cov.:

AF XY:

0.000846

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00184

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00141

Hom.:

Bravo

AF:

0.000846

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000692

AC:

EpiCase

AF:

0.00169

EpiControl

AF:

0.00130

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

Mar 07, 2023

The c.780C>A (p.D260E) alteration is located in exon 8 (coding exon 8) of the BPIFB3 gene. This alteration results from a C to A substitution at nucleotide position 780, causing the aspartic acid (D) at amino acid position 260 to be replaced by a glutamic acid (E). 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

0.20

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.37

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.052

Eigen

Benign

0.085

Eigen_PC

Benign

0.024

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.65

M_CAP

Benign

0.0047

MetaRNN

Benign

0.083

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

0.74

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.91

REVEL

Benign

0.23

Sift

Benign

0.28

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.46

MutPred

0.59

Gain of methylation at K263 (P = 0.0963);

MVP

0.50

MPC

0.47

ClinPred

0.036

GERP RS

2.0

Varity_R

0.057

gMVP

0.060

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