Variant 20-33225206-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_178466.5(BPIFA3):c.495C>A(p.Cys165*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000896 in 1,614,072 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Benign (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0043 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00054 ( 5 hom. )

Consequence

BPIFA3
NM_178466.5 stop_gained

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.00700

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 -9 ACMG points.

BP6

Variant 20-33225206-C-A is Benign according to our data. Variant chr20-33225206-C-A is described in ClinVar as [Benign]. Clinvar id is 3040241.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000543 (794/1461836) while in subpopulation AFR AF= 0.0168 (564/33480). AF 95% confidence interval is 0.0157. There are 5 homozygotes in gnomad4_exome. There are 358 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 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.495C>A	p.Cys165*	stop_gained	4/7	ENST00000375454.8	NP_848561.2	Q9BQP9-1
BPIFA3	NM_001042439.2 linkuse as main transcript	c.387C>A	p.Cys129*	stop_gained	3/6		NP_001035904.1	Q9BQP9-2
BPIFA3	XR_244132.4 linkuse as main transcript	n.722C>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.495C>A	p.Cys165*	stop_gained	4/7	5	NM_178466.5	ENSP00000364603.3	Q9BQP9-1
BPIFA3	ENST00000375452.3 linkuse as main transcript	c.387C>A	p.Cys129*	stop_gained	3/6	1		ENSP00000364601.3	Q9BQP9-2
BPIFA3	ENST00000490499.5 linkuse as main transcript	n.874C>A		non_coding_transcript_exon_variant	5/7	1
BPIFA3	ENST00000471233.1 linkuse as main transcript	n.705C>A		non_coding_transcript_exon_variant	4/7	5

Frequencies

GnomAD3 genomes

AF:

0.00425

AC:

646

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00118

AC:

297

AN:

251352

Hom.:

AF XY:

0.000987

AC XY:

134

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.0148

Gnomad AMR exome

AF:

0.000983

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000543

AC:

794

AN:

1461836

Hom.:

Cov.:

AF XY:

0.000492

AC XY:

358

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0168

Gnomad4 AMR exome

AF:

0.00119

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000890

Gnomad4 OTH exome

AF:

0.00113

GnomAD4 genome

AF:

0.00428

AC:

652

AN:

152236

Hom.:

Cov.:

AF XY:

0.00417

AC XY:

310

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0148

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.000609

Hom.:

Bravo

AF:

0.00476

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0157

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00143

AC:

173

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000218

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

Dec 28, 2021

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

BayesDel_addAF

Uncertain

0.016

BayesDel_noAF

Pathogenic

0.26

CADD

Pathogenic

DANN

Uncertain

0.98

Eigen

Benign

-0.040

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.043

Vest4

0.31

GERP RS

1.5

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