rs17304572

chr20-33174113-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080574.4(BPIFA2):c.337A>G(p.Lys113Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00849 in 1,614,144 control chromosomes in the GnomAD database, including 198 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0083 (18 hom., cov: 32)
  • Exomes 𝑓: 0.0085 (180 hom.)
• Consequence: BPIFA2 NM_080574.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.417

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026183426).
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BPIFA2	NM_080574.4	c.337A>G	p.Lys113Glu	missense_variant	4/9	ENST00000354932.6
BPIFA2	NM_001319164.2	c.337A>G	p.Lys113Glu	missense_variant	4/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BPIFA2	ENST00000354932.6	c.337A>G	p.Lys113Glu	missense_variant	4/9	1	NM_080574.4	P1
BPIFA2	ENST00000253362.6	c.337A>G	p.Lys113Glu	missense_variant	4/9	1		P1

Frequencies

GnomAD3 genomes AF: 0.00821 AC: 1250 AN: 152180 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.00251

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0403

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00707

Gnomad OTH AF: 0.00861

GnomAD3 exomes AF: 0.0146 AC: 3680 AN: 251474 Hom.: 122 AF XY: 0.0119 AC XY: 1613 AN XY: 135904

Gnomad AFR exome AF: 0.00215

Gnomad AMR exome AF: 0.0754

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00140

Gnomad FIN exome AF: 0.00249

Gnomad NFE exome AF: 0.00763

Gnomad OTH exome AF: 0.0112

GnomAD4 exome AF: 0.00851 AC: 12439 AN: 1461846 Hom.: 180 Cov.: 30 AF XY: 0.00786 AC XY: 5719 AN XY: 727222

Gnomad4 AFR exome AF: 0.00140

Gnomad4 AMR exome AF: 0.0732

Gnomad4 ASJ exome AF: 0.000574

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00147

Gnomad4 FIN exome AF: 0.00324

Gnomad4 NFE exome AF: 0.00754

Gnomad4 OTH exome AF: 0.00694

GnomAD4 genome AF: 0.00827 AC: 1260 AN: 152298 Hom.: 18 Cov.: 32 AF XY: 0.00823 AC XY: 613 AN XY: 74478

Gnomad4 AFR AF: 0.00250

Gnomad4 AMR AF: 0.0409

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00217

Gnomad4 NFE AF: 0.00707

Gnomad4 OTH AF: 0.00852

Alfa AF: 0.00840 Hom.: 32

Bravo AF: 0.0119

TwinsUK AF: 0.00593 AC: 22

ALSPAC AF: 0.00778 AC: 30

ESP6500AA AF: 0.00204 AC: 9

ESP6500EA AF: 0.00756 AC: 65

ExAC AF: 0.0129 AC: 1562

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.00480

EpiControl AF: 0.00622

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.72
Cadd	Benign	17
Dann	Uncertain	0.99
DEOGEN2	Benign	0.00071	T;T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.021	N
MetaRNN	Benign	0.0026	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.71	N;N
REVEL	Benign	0.030
Sift	Benign	0.072	T;T
Sift4G	Benign	0.096	T;T
Polyphen		0.76	P;P
Vest4		0.040
MPC		0.46
ClinPred		0.023	T
GERP RS		0.54
Varity_R		0.072
gMVP		0.12

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: rs17304572; hg19: chr20-31761919;