Variant 20-33225105-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_178466.5(BPIFA3):c.394G>A(p.Asp132Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000163 in 1,613,932 control chromosomes in the GnomAD database, including 1 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 (★).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

BPIFA3
NM_178466.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.836

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.014087558).

BP6

Variant 20-33225105-G-A is Benign according to our data. Variant chr20-33225105-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3134818.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPIFA3	NM_178466.5 linkuse as main transcript	c.394G>A	p.Asp132Asn	missense_variant	4/7	ENST00000375454.8	NP_848561.2	Q9BQP9-1
BPIFA3	NM_001042439.2 linkuse as main transcript	c.286G>A	p.Asp96Asn	missense_variant	3/6		NP_001035904.1	Q9BQP9-2
BPIFA3	XR_244132.4 linkuse as main transcript	n.621G>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.394G>A	p.Asp132Asn	missense_variant	4/7	5	NM_178466.5	ENSP00000364603.3	Q9BQP9-1
BPIFA3	ENST00000375452.3 linkuse as main transcript	c.286G>A	p.Asp96Asn	missense_variant	3/6	1		ENSP00000364601.3	Q9BQP9-2
BPIFA3	ENST00000490499.5 linkuse as main transcript	n.773G>A		non_coding_transcript_exon_variant	5/7	1
BPIFA3	ENST00000471233.1 linkuse as main transcript	n.604G>A		non_coding_transcript_exon_variant	4/7	5

Frequencies

GnomAD3 genomes

AF:

0.000441

AC:

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000831

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000962

GnomAD3 exomes

AF:

0.000267

AC:

AN:

251112

Hom.:

AF XY:

0.000251

AC XY:

AN XY:

135710

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00108

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000705

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000134

AC:

196

AN:

1461780

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

116

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00108

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000351

Gnomad4 OTH exome

AF:

0.000281

GnomAD4 genome

AF:

0.000440

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.00133

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000832

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000951

Alfa

AF:

0.000105

Hom.:

Bravo

AF:

0.000514

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000264

AC:

Asia WGS

AF:

0.00260

AC:

AN:

3476

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 10, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.3

DANN

Benign

0.62

DEOGEN2

Benign

0.0013

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0043

LIST_S2

Benign

0.53

T;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.46

N;.

PrimateAI

Benign

0.35

PROVEAN

Benign

0.17

N;N

REVEL

Benign

0.024

Sift

Benign

0.58

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0050

B;B

Vest4

0.12

MVP

0.067

MPC

0.020

ClinPred

0.0044

GERP RS

-0.14

Varity_R

0.035

gMVP

0.050

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