20-33179593-TC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_080574.4(BPIFA2):c.646-9del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00299 in 1,604,676 control chromosomes in the GnomAD database, including 110 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (46 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (64 hom.)
• Consequence: BPIFA2 NM_080574.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.181

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 -10 ACMG points.

• BP6: Variant 20-33179593-TC-T is Benign according to our data. Variant chr20-33179593-TC-T is described in ClinVar as [Benign]. Clinvar id is 777540.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BPIFA2	NM_080574.4	c.646-9del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000354932.6
BPIFA2	NM_001319164.2	c.646-9del		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BPIFA2	ENST00000354932.6	c.646-9del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_080574.4	P1
BPIFA2	ENST00000253362.6	c.646-9del		splice_polypyrimidine_tract_variant, intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.0142 AC: 2158 AN: 152146 Hom.: 45 Cov.: 32

Gnomad AFR AF: 0.0488

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.00416 AC: 1047 AN: 251466 Hom.: 32 AF XY: 0.00312 AC XY: 424 AN XY: 135902

Gnomad AFR exome AF: 0.0534

Gnomad AMR exome AF: 0.00240

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000598

Gnomad OTH exome AF: 0.00293

GnomAD4 exome AF: 0.00180 AC: 2620 AN: 1452412 Hom.: 64 Cov.: 30 AF XY: 0.00161 AC XY: 1164 AN XY: 723086

Gnomad4 AFR exome AF: 0.0532

Gnomad4 AMR exome AF: 0.00282

Gnomad4 ASJ exome AF: 0.000192

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000302

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000382

Gnomad4 OTH exome AF: 0.00408

GnomAD4 genome AF: 0.0143 AC: 2171 AN: 152264 Hom.: 46 Cov.: 32 AF XY: 0.0141 AC XY: 1051 AN XY: 74472

Gnomad4 AFR AF: 0.0490

Gnomad4 AMR AF: 0.00464

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000544

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00835 Hom.: 4

Bravo AF: 0.0164

Asia WGS AF: 0.00549 AC: 20 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs149853875; hg19: chr20-31767399;