20-33179649-G-A

Position:

• chr20-33179649-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_080574.4(BPIFA2):​c.691G>A​(p.Val231Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BPIFA2 NM_080574.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.63

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]

ACMG classification

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=0.048771977).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPIFA2	NM_080574.4	c.691G>A	p.Val231Ile	missense_variant	7/9	ENST00000354932.6	NP_542141.1
BPIFA2	NM_001319164.2	c.691G>A	p.Val231Ile	missense_variant	7/9		NP_001306093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BPIFA2	ENST00000354932.6	c.691G>A	p.Val231Ile	missense_variant	7/9	1	NM_080574.4	ENSP00000347012.5
BPIFA2	ENST00000253362.6	c.691G>A	p.Val231Ile	missense_variant	7/9	1		ENSP00000253362.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2024

The c.691G>A (p.V231I) alteration is located in exon 7 (coding exon 6) of the BPIFA2 gene. This alteration results from a G to A substitution at nucleotide position 691, causing the valine (V) at amino acid position 231 to be replaced by an isoleucine (I). 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	0.079
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.0010
DANN	Benign	0.36
DEOGEN2	Benign	0.00086	T;T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.34	.;T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.049	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.20	N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.29	N;N
REVEL	Benign	0.017
Sift	Benign	0.58	T;T
Sift4G	Benign	0.95	T;T
Polyphen		0.0010	B;B
Vest4		0.044
MutPred		0.48		Gain of catalytic residue at V231 (P = 0.1215);Gain of catalytic residue at V231 (P = 0.1215);
MVP		0.048
MPC		0.057
ClinPred		0.074	T
GERP RS		-6.5
Varity_R		0.017
gMVP		0.028

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-31767455;