rs1078761

Positions:

• chr20-33288875-A-C
• chr20-33288875-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033197.3(BPIFB1):​c.250A>C​(p.Ile84Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. I84V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BPIFB1 NM_033197.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.666

Genes affected

BPIFB1 (HGNC:16108): (BPI fold containing family B member 1) The protein encoded by this gene may be involved in the innate immune response to bacterial exposure in the mouth, nasal cavities, and lungs. The encoded protein is secreted and is a member of the BPI/LBP/PLUNC protein superfamily. This gene is found with other members of the superfamily in a cluster on chromosome 20. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12371299).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPIFB1	NM_033197.3	c.250A>C	p.Ile84Leu	missense_variant	3/16	ENST00000253354.2	NP_149974.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BPIFB1	ENST00000253354.2	c.250A>C	p.Ile84Leu	missense_variant	3/16	1	NM_033197.3	ENSP00000253354.1
BPIFB1	ENST00000423645.5	c.250A>C	p.Ile84Leu	missense_variant	3/5	3		ENSP00000390471.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000405 AC: 1 AN: 246746 Hom.: 0 AF XY: 0.00000747 AC XY: 1 AN XY: 133790

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000907

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	10
DANN	Benign	0.90
DEOGEN2	Benign	0.061	T;T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	.;M
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.11
Sift	Uncertain	0.013	D;D
Sift4G	Uncertain	0.029	D;D
Polyphen		0.51	.;P
Vest4		0.34
MutPred		0.59		Gain of catalytic residue at I84 (P = 0.0069);Gain of catalytic residue at I84 (P = 0.0069);
MVP		0.030
MPC		0.39
ClinPred		0.25	T
GERP RS		1.8
Varity_R		0.11
gMVP		0.26

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: rs1078761; hg19: chr20-31876681;