Variant 20-33172932-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_080574.4(BPIFA2):c.158G>A(p.Gly53Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000472 in 1,611,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

BPIFA2
NM_080574.4 missense, splice_region

Scores

Splicing: ADA: 0.005604

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.19

Variant links:

Genes affected

BPIFA2 (HGNC:16203): (BPI fold containing family A member 2) This gene encodes a member of the palate, lung and nasal epithelium clone (Plunc) family of proteins. Members of this family have been proposed to play a role in the local antibacterial response in nose, mouth and upper respiratory pathways. The encoded soluble salivary protein binds bacterial lipopolysaccharide (LPS) and inhibits bacterial growth. This gene is present in a gene cluster on chromosome 20. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

BPIFA2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.015041649).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPIFA2	NM_080574.4 linkuse as main transcript	c.158G>A	p.Gly53Asp	missense_variant, splice_region_variant	3/9	ENST00000354932.6	NP_542141.1	Q96DR5A8K739
BPIFA2	NM_001319164.2 linkuse as main transcript	c.158G>A	p.Gly53Asp	missense_variant, splice_region_variant	3/9		NP_001306093.1	Q96DR5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BPIFA2	ENST00000354932.6 linkuse as main transcript	c.158G>A	p.Gly53Asp	missense_variant, splice_region_variant	3/9	1	NM_080574.4	ENSP00000347012.5		Q96DR5
BPIFA2	ENST00000253362.6 linkuse as main transcript	c.158G>A	p.Gly53Asp	missense_variant, splice_region_variant	3/9	1		ENSP00000253362.2		Q96DR5

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000685

AC:

AN:

248032

Hom.:

AF XY:

0.0000447

AC XY:

AN XY:

134124

show subpopulations

Gnomad AFR exome

AF:

0.000987

Gnomad AMR exome

AF:

0.0000297

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000288

AC:

AN:

1459054

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

725828

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.0000453

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.000223

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.000818

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000483

Hom.:

Bravo

AF:

0.000298

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000988

AC:

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

Jul 30, 2023

The c.158G>A (p.G53D) alteration is located in exon 3 (coding exon 2) of the BPIFA2 gene. This alteration results from a G to A substitution at nucleotide position 158, causing the glycine (G) at amino acid position 53 to be replaced by an aspartic acid (D). 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

0.088

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.036

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0015

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0044

LIST_S2

Benign

0.30

.;T

M_CAP

Benign

0.0037

MetaRNN

Benign

0.015

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.5

L;L

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.59

N;N

REVEL

Benign

0.0090

Sift

Benign

0.15

T;T

Sift4G

Benign

0.20

T;T

Polyphen

0.012

B;B

Vest4

0.12

MVP

0.076

MPC

0.088

ClinPred

0.028

GERP RS

-4.2

Varity_R

0.041

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0056

dbscSNV1_RF

Benign

0.23

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