chr20-33180525-C-G

Variant names:

• chr20-33180525-C-G
• rs143444594
• NM_080574.4:c.715C>G

Variant summary

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

The NM_080574.4(BPIFA2):​c.715C>G​(p.Pro239Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,914 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BPIFA2 NM_080574.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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=0.047855794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BPIFA2	NM_080574.4	c.715C>G	p.Pro239Ala	missense_variant	Exon 8 of 9	ENST00000354932.6	NP_542141.1
BPIFA2	NM_001319164.2	c.715C>G	p.Pro239Ala	missense_variant	Exon 8 of 9		NP_001306093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BPIFA2	ENST00000354932.6	c.715C>G	p.Pro239Ala	missense_variant	Exon 8 of 9	1	NM_080574.4	ENSP00000347012.5
BPIFA2	ENST00000253362.6	c.715C>G	p.Pro239Ala	missense_variant	Exon 8 of 9	1		ENSP00000253362.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251374 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135878

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460914 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726888

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000193 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.036
DANN	Benign	0.086
DEOGEN2	Benign	0.00025	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.33	.;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.048	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L;L
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.80	N;N
REVEL	Benign	0.0080
Sift	Benign	0.38	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0010	B;B
Vest4		0.14
MutPred		0.30		Loss of methylation at K242 (P = 0.0778);Loss of methylation at K242 (P = 0.0778);
MVP		0.040
MPC		0.066
ClinPred		0.058	T
GERP RS		-2.1
Varity_R		0.015
gMVP		0.034

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

Other links and lift over

dbSNP: rs143444594; hg19: chr20-31768331;