20-33174079-G-T

Position:

• chr20-33174079-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_080574.4(BPIFA2):​c.303G>T​(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 0.00108 in 1,613,708 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0049 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00068 (9 hom.)
• Consequence: BPIFA2 NM_080574.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.8688
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0190

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 20-33174079-G-T is Benign according to our data. Variant chr20-33174079-G-T is described in ClinVar as [Benign]. Clinvar id is 780074.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.019 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0049 (747/152310) while in subpopulation AFR AF= 0.0167 (694/41552). AF 95% confidence interval is 0.0157. There are 5 homozygotes in gnomad4. There are 351 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/exons	MANE	Protein	UniProt
BPIFA2	NM_080574.4	c.303G>T	p.Gly101Gly	splice_region_variant, synonymous_variant	4/9	ENST00000354932.6	NP_542141.1
BPIFA2	NM_001319164.2	c.303G>T	p.Gly101Gly	splice_region_variant, synonymous_variant	4/9		NP_001306093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BPIFA2	ENST00000354932.6	c.303G>T	p.Gly101Gly	splice_region_variant, synonymous_variant	4/9	1	NM_080574.4	ENSP00000347012.5
BPIFA2	ENST00000253362.6	c.303G>T	p.Gly101Gly	splice_region_variant, synonymous_variant	4/9	1		ENSP00000253362.2

Frequencies

GnomAD3 genomes AF: 0.00490 AC: 746 AN: 152192 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0167

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00149 AC: 375 AN: 251460 Hom.: 3 AF XY: 0.00108 AC XY: 147 AN XY: 135902

Gnomad AFR exome AF: 0.0180

Gnomad AMR exome AF: 0.000925

Gnomad ASJ exome AF: 0.000496

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000299

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.000683 AC: 998 AN: 1461398 Hom.: 9 Cov.: 30 AF XY: 0.000634 AC XY: 461 AN XY: 727044

Gnomad4 AFR exome AF: 0.0182

Gnomad4 AMR exome AF: 0.00112

Gnomad4 ASJ exome AF: 0.000268

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000928

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000201

Gnomad4 OTH exome AF: 0.00146

GnomAD4 genome AF: 0.00490 AC: 747 AN: 152310 Hom.: 5 Cov.: 32 AF XY: 0.00471 AC XY: 351 AN XY: 74484

Gnomad4 AFR AF: 0.0167

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.0000574 Hom.: 2

Bravo AF: 0.00584

EpiCase AF: 0.000491

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.6
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.87
dbscSNV1_RF	Benign	0.55
SpliceAI score (max)		0.17		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: rs61734343; hg19: chr20-31761885;