20-33288875-A-G

Variant names:

• chr20-33288875-A-G
• rs1078761
• NM_033197.3:c.250A>G

Variant summary

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

The NM_033197.3(BPIFB1):​c.250A>G​(p.Ile84Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 1,612,544 control chromosomes in the GnomAD database, including 65,697 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (9037 hom., cov: 32)
  • Exomes 𝑓: 0.27 (56660 hom.)
• Consequence: BPIFB1 NM_033197.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.666
• Publications: 25 publications found

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

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

• BP4: Computational evidence support a benign effect (MetaRNN=4.6303868E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033197.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPIFB1	NM_033197.3	MANE Select	c.250A>G	p.Ile84Val	missense	Exon 3 of 16	NP_149974.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPIFB1	ENST00000253354.2	TSL:1 MANE Select	c.250A>G	p.Ile84Val	missense	Exon 3 of 16	ENSP00000253354.1
	BPIFB1	ENST00000423645.5	TSL:3	c.250A>G	p.Ile84Val	missense	Exon 3 of 5	ENSP00000390471.1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50592 AN: 152004 Hom.: 9019 Cov.: 32

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.316

GnomAD2 exomes AF: 0.301 AC: 74153 AN: 246746 AF XY: 0.289

Gnomad AFR exome AF: 0.465

Gnomad AMR exome AF: 0.435

Gnomad ASJ exome AF: 0.358

Gnomad EAS exome AF: 0.232

Gnomad FIN exome AF: 0.269

Gnomad NFE exome AF: 0.277

Gnomad OTH exome AF: 0.287

GnomAD4 exome AF: 0.274 AC: 399977 AN: 1460422 Hom.: 56660 Cov.: 34 AF XY: 0.271 AC XY: 196816 AN XY: 726542

African (AFR) AF: 0.467 AC: 15630 AN: 33470

American (AMR) AF: 0.427 AC: 19039 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 9305 AN: 26122

East Asian (EAS) AF: 0.246 AC: 9747 AN: 39680

South Asian (SAS) AF: 0.191 AC: 16479 AN: 86202

European-Finnish (FIN) AF: 0.266 AC: 13985 AN: 52596

Middle Eastern (MID) AF: 0.326 AC: 1880 AN: 5766

European-Non Finnish (NFE) AF: 0.267 AC: 296939 AN: 1111602

Other (OTH) AF: 0.281 AC: 16973 AN: 60364

GnomAD4 genome AF: 0.333 AC: 50666 AN: 152122 Hom.: 9037 Cov.: 32 AF XY: 0.330 AC XY: 24555 AN XY: 74370

African (AFR) AF: 0.458 AC: 18989 AN: 41458

American (AMR) AF: 0.377 AC: 5773 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1247 AN: 3468

East Asian (EAS) AF: 0.236 AC: 1222 AN: 5168

South Asian (SAS) AF: 0.197 AC: 951 AN: 4830

European-Finnish (FIN) AF: 0.266 AC: 2815 AN: 10598

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18648 AN: 67986

Other (OTH) AF: 0.318 AC: 671 AN: 2112

Alfa AF: 0.290 Hom.: 28608

Bravo AF: 0.352

TwinsUK AF: 0.264 AC: 978

ALSPAC AF: 0.259 AC: 998

ESP6500AA AF: 0.446 AC: 1964

ESP6500EA AF: 0.288 AC: 2478

ExAC AF: 0.294 AC: 35680

Asia WGS AF: 0.248 AC: 864 AN: 3478

EpiCase AF: 0.283

EpiControl AF: 0.280

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.8
DANN	Benign	0.34
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.00046	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.67
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.036
Sift	Benign	0.16	T
Sift4G	Benign	0.13	T
Polyphen		0.016	B
Vest4		0.040
MPC		0.18
ClinPred		0.0035	T
GERP RS		1.8
Varity_R		0.036
gMVP		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1078761; hg19: chr20-31876681; COSMIC: COSV53607188;