NM_080574.4:c.706G>T

Variant names:

• chr20-33179664-G-T
• NM_080574.4:c.706G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080574.4(BPIFA2):​c.706G>T​(p.Val236Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,380 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: BPIFA2 NM_080574.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.394

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0743337).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BPIFA2	NM_080574.4	c.706G>T	p.Val236Phe	missense_variant	Exon 7 of 9	ENST00000354932.6	NP_542141.1
BPIFA2	NM_001319164.2	c.706G>T	p.Val236Phe	missense_variant	Exon 7 of 9		NP_001306093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BPIFA2	ENST00000354932.6	c.706G>T	p.Val236Phe	missense_variant	Exon 7 of 9	1	NM_080574.4	ENSP00000347012.5
BPIFA2	ENST00000253362.6	c.706G>T	p.Val236Phe	missense_variant	Exon 7 of 9	1		ENSP00000253362.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1457380 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725370

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000271

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.706G>T (p.V236F) alteration is located in exon 7 (coding exon 6) of the BPIFA2 gene. This alteration results from a G to T substitution at nucleotide position 706, causing the valine (V) at amino acid position 236 to be replaced by a phenylalanine (F). 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	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	3.3
DANN	Benign	0.83
DEOGEN2	Benign	0.014	T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0058	N
LIST_S2	Benign	0.34	.;T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.074	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.34	N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.055
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.049	D;D
Polyphen		0.20	B;B
Vest4		0.15
MutPred		0.35		Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);
MVP		0.067
MPC		0.088
ClinPred		0.66	D
GERP RS		-4.0
Varity_R		0.074
gMVP		0.16

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: chr20-31767470;