Variant 20-33226471-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_178466.5(BPIFA3):c.602C>T(p.Pro201Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,609,456 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0096 ( 20 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 51 hom. )

Consequence

BPIFA3
NM_178466.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.97

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008552313).

BP6

Variant 20-33226471-C-T is Benign according to our data. Variant chr20-33226471-C-T is described in ClinVar as [Benign]. Clinvar id is 3037591.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00963 (1465/152078) while in subpopulation EAS AF= 0.0351 (182/5186). AF 95% confidence interval is 0.0309. There are 20 homozygotes in gnomad4. There are 699 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPIFA3	NM_178466.5 linkuse as main transcript	c.602C>T	p.Pro201Leu	missense_variant	5/7	ENST00000375454.8	NP_848561.2	Q9BQP9-1
BPIFA3	NM_001042439.2 linkuse as main transcript	c.494C>T	p.Pro165Leu	missense_variant	4/6		NP_001035904.1	Q9BQP9-2
BPIFA3	XR_244132.4 linkuse as main transcript	n.829C>T		non_coding_transcript_exon_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BPIFA3	ENST00000375454.8 linkuse as main transcript	c.602C>T	p.Pro201Leu	missense_variant	5/7	5	NM_178466.5	ENSP00000364603.3	Q9BQP9-1
BPIFA3	ENST00000375452.3 linkuse as main transcript	c.494C>T	p.Pro165Leu	missense_variant	4/6	1		ENSP00000364601.3	Q9BQP9-2
BPIFA3	ENST00000490499.5 linkuse as main transcript	n.2139C>T		non_coding_transcript_exon_variant	5/7	1
BPIFA3	ENST00000471233.1 linkuse as main transcript	n.812C>T		non_coding_transcript_exon_variant	5/7	5

Frequencies

GnomAD3 genomes

AF:

0.00955

AC:

1451

AN:

151960

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0285

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0348

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00493

AC:

1225

AN:

248580

Hom.:

AF XY:

0.00422

AC XY:

566

AN XY:

134248

show subpopulations

Gnomad AFR exome

AF:

0.0306

Gnomad AMR exome

AF:

0.00251

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0310

Gnomad SAS exome

AF:

0.00114

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000248

Gnomad OTH exome

AF:

0.00247

GnomAD4 exome

AF:

0.00200

AC:

2910

AN:

1457378

Hom.:

Cov.:

AF XY:

0.00190

AC XY:

1374

AN XY:

724970

show subpopulations

Gnomad4 AFR exome

AF:

0.0314

Gnomad4 AMR exome

AF:

0.00241

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.0295

Gnomad4 SAS exome

AF:

0.00116

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000175

Gnomad4 OTH exome

AF:

0.00423

GnomAD4 genome

AF:

0.00963

AC:

1465

AN:

152078

Hom.:

Cov.:

AF XY:

0.00941

AC XY:

699

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.0287

Gnomad4 AMR

AF:

0.00275

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0351

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00311

Hom.:

Bravo

AF:

0.0111

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0288

AC:

127

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00531

AC:

645

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

BPIFA3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 31, 2019

This variant is classified as 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

0.29

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.059

T;.

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.83

T;T

MetaRNN

Benign

0.0086

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;.

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-7.1

D;D

REVEL

Benign

0.22

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.83

MVP

0.29

MPC

0.17

ClinPred

0.042

GERP RS

3.8

Varity_R

0.46

gMVP

0.54

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