chr20-33235824-T-C

Variant names:

• chr20-33235824-T-C
• rs750064
• NM_130852.3:c.-242T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130852.3(BPIFA1):​c.-242T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 152,086 control chromosomes in the GnomAD database, including 27,810 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (27810 hom., cov: 31)
• Consequence: BPIFA1 NM_130852.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240
• Publications: 9 publications found

Genes affected

BPIFA1 (HGNC:15749): (BPI fold containing family A member 1) This gene is the human homolog of murine plunc, and like the mouse gene, is specifically expressed in the upper airways and nasopharyngeal regions. The encoded antimicrobial protein displays antibacterial activity against Gram-negative bacteria. It is thought to be involved in inflammatory responses to irritants in the upper airways and may also serve as a potential molecular marker for detection of micrometastasis in non-small-cell lung cancer. Multiple transcript variants resulting from alternative splicing in the 3' UTR have been detected, but the full-length nature of only three are known. [provided by RefSeq, Aug 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BPIFA1	NM_130852.3	c.-242T>C		upstream_gene_variant		ENST00000354297.9	NP_570913.1
BPIFA1	NM_001243193.2	c.-242T>C		upstream_gene_variant			NP_001230122.1
BPIFA1	NM_016583.4	c.-242T>C		upstream_gene_variant			NP_057667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BPIFA1	ENST00000354297.9	c.-242T>C		upstream_gene_variant		1	NM_130852.3	ENSP00000346251.4
BPIFA1	ENST00000375413.8	c.-242T>C		upstream_gene_variant		1		ENSP00000364562.4
BPIFA1	ENST00000375422.6	c.-242T>C		upstream_gene_variant		1		ENSP00000364571.2

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87720 AN: 151968 Hom.: 27746 Cov.: 31

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.531

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.578 AC: 87854 AN: 152086 Hom.: 27810 Cov.: 31 AF XY: 0.571 AC XY: 42475 AN XY: 74354

African (AFR) AF: 0.859 AC: 35626 AN: 41496

American (AMR) AF: 0.516 AC: 7883 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1636 AN: 3468

East Asian (EAS) AF: 0.384 AC: 1985 AN: 5164

South Asian (SAS) AF: 0.375 AC: 1808 AN: 4818

European-Finnish (FIN) AF: 0.472 AC: 4997 AN: 10580

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32179 AN: 67960

Other (OTH) AF: 0.535 AC: 1133 AN: 2116

Alfa AF: 0.518 Hom.: 59579

Bravo AF: 0.599

Asia WGS AF: 0.451 AC: 1569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.79
PhyloP100		0.024
PromoterAI		-0.032	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs750064; hg19: chr20-31823630;