Genetic Variant NM_080574.4:c.303G>A (chr20-33174079-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BS1BS2

The NM_080574.4(BPIFA2):c.303G>A(p.Gly101Gly) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00091 in 1,613,716 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0013 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00087 ( 22 hom. )

Consequence

BPIFA2
NM_080574.4 splice_region, synonymous

Scores

Splicing: ADA: 0.01132

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0190

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP7

Synonymous conserved (PhyloP=0.019 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00125 (191/152314) while in subpopulation EAS AF= 0.0335 (174/5190). AF 95% confidence interval is 0.0295. There are 5 homozygotes in gnomad4. There are 100 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BPIFA2	NM_080574.4 link	c.303G>A	p.Gly101Gly	splice_region_variant, synonymous_variant	Exon 4 of 9	ENST00000354932.6	NP_542141.1	Q96DR5A8K739
BPIFA2	NM_001319164.2 link	c.303G>A	p.Gly101Gly	splice_region_variant, synonymous_variant	Exon 4 of 9		NP_001306093.1	Q96DR5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BPIFA2	ENST00000354932.6 link	c.303G>A	p.Gly101Gly	splice_region_variant, synonymous_variant	Exon 4 of 9	1	NM_080574.4	ENSP00000347012.5		Q96DR5
BPIFA2	ENST00000253362.6 link	c.303G>A	p.Gly101Gly	splice_region_variant, synonymous_variant	Exon 4 of 9	1		ENSP00000253362.2		Q96DR5

Frequencies

GnomAD3 genomes

AF:

0.00125

AC:

190

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0333

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00227

AC:

572

AN:

251460

Hom.:

AF XY:

0.00211

AC XY:

287

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0294

Gnomad SAS exome

AF:

0.000555

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000874

AC:

1277

AN:

1461402

Hom.:

Cov.:

AF XY:

0.000860

AC XY:

625

AN XY:

727046

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0277

Gnomad4 SAS exome

AF:

0.000638

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000414

Gnomad4 OTH exome

AF:

0.00114

GnomAD4 genome

AF:

0.00125

AC:

191

AN:

152314

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

100

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0335

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00211

Hom.:

Bravo

AF:

0.00151

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

3.6

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.011

dbscSNV1_RF

Benign

0.18

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over