Variant 20-33225207-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_178466.5(BPIFA3):c.496G>A(p.Asp166Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00194 in 1,614,086 control chromosomes in the GnomAD database, including 6 homozygotes. 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 Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 6 hom. )

Consequence

BPIFA3
NM_178466.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -3.73

Variant links:

Genes affected

BPIFA3 (HGNC:16204): (BPI fold containing family A member 3) Predicted to enable lipid binding activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

BPIFA3 links:

BPIFA3 (HGNC:):

BPIFA3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010327339).

BP6

Variant 20-33225207-G-A is Benign according to our data. Variant chr20-33225207-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3041043.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPIFA3	NM_178466.5 linkuse as main transcript	c.496G>A	p.Asp166Asn	missense_variant	4/7	ENST00000375454.8	NP_848561.2	Q9BQP9-1
BPIFA3	NM_001042439.2 linkuse as main transcript	c.388G>A	p.Asp130Asn	missense_variant	3/6		NP_001035904.1	Q9BQP9-2
BPIFA3	XR_244132.4 linkuse as main transcript	n.723G>A		non_coding_transcript_exon_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BPIFA3	ENST00000375454.8 linkuse as main transcript	c.496G>A	p.Asp166Asn	missense_variant	4/7	5	NM_178466.5	ENSP00000364603.3	Q9BQP9-1
BPIFA3	ENST00000375452.3 linkuse as main transcript	c.388G>A	p.Asp130Asn	missense_variant	3/6	1		ENSP00000364601.3	Q9BQP9-2
BPIFA3	ENST00000490499.5 linkuse as main transcript	n.875G>A		non_coding_transcript_exon_variant	5/7	1
BPIFA3	ENST00000471233.1 linkuse as main transcript	n.706G>A		non_coding_transcript_exon_variant	4/7	5

Frequencies

GnomAD3 genomes

AF:

0.00110

AC:

167

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00182

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00127

AC:

318

AN:

251356

Hom.:

AF XY:

0.00133

AC XY:

180

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.000596

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00206

Gnomad FIN exome

AF:

0.000462

Gnomad NFE exome

AF:

0.00176

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00203

AC:

2970

AN:

1461838

Hom.:

Cov.:

AF XY:

0.00202

AC XY:

1468

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.000581

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00205

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.00233

Gnomad4 OTH exome

AF:

0.00212

GnomAD4 genome

AF:

0.00110

AC:

167

AN:

152248

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.00182

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00184

Hom.:

Bravo

AF:

0.00108

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.00114

AC:

139

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00207

EpiControl

AF:

0.00184

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

BPIFA3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 01, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.0080

DANN

Benign

0.60

DEOGEN2

Benign

0.00039

T;.

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0045

LIST_S2

Benign

0.19

T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

N;.

PrimateAI

Benign

0.25

PROVEAN

Benign

0.67

N;N

REVEL

Benign

0.014

Sift

Benign

0.51

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.12

MVP

0.055

MPC

0.020

ClinPred

0.0020

GERP RS

-5.5

Varity_R

0.023

gMVP

0.11

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