rs2070325

Positions:

• chr20-33086040-A-G
• chr20-33086040-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182519.3(BPIFB4):​c.802A>G​(p.Ile268Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 1,610,064 control chromosomes in the GnomAD database, including 123,985 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.36 (10889 hom., cov: 32)
  • Exomes 𝑓: 0.38 (113096 hom.)
• Consequence: BPIFB4 NM_182519.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.82

Genes affected

BPIFB4 (HGNC:16179): (BPI fold containing family B member 4) Predicted to enable lipid binding activity. Predicted to be located in cytoplasm and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.7507998E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPIFB4	NM_182519.3	c.802A>G	p.Ile268Val	missense_variant	7/18	ENST00000375483.4	NP_872325.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BPIFB4	ENST00000375483.4	c.802A>G	p.Ile268Val	missense_variant	7/18	5	NM_182519.3	ENSP00000364632.3
BPIFB4	ENST00000674031.1	c.1168A>G	p.Ile390Val	missense_variant	4/15			ENSP00000501266.1
BPIFB4	ENST00000445356.1	n.107-2926A>G		intron_variant		2		ENSP00000388423.1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55233 AN: 151874 Hom.: 10895 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.365

GnomAD3 exomes AF: 0.414 AC: 104036 AN: 251404 Hom.: 23707 AF XY: 0.414 AC XY: 56196 AN XY: 135876

Gnomad AFR exome AF: 0.264

Gnomad AMR exome AF: 0.440

Gnomad ASJ exome AF: 0.262

Gnomad EAS exome AF: 0.800

Gnomad SAS exome AF: 0.479

Gnomad FIN exome AF: 0.437

Gnomad NFE exome AF: 0.358

Gnomad OTH exome AF: 0.390

GnomAD4 exome AF: 0.385 AC: 560965 AN: 1458072 Hom.: 113096 Cov.: 42 AF XY: 0.386 AC XY: 279725 AN XY: 724562

Gnomad4 AFR exome AF: 0.259

Gnomad4 AMR exome AF: 0.439

Gnomad4 ASJ exome AF: 0.267

Gnomad4 EAS exome AF: 0.789

Gnomad4 SAS exome AF: 0.473

Gnomad4 FIN exome AF: 0.430

Gnomad4 NFE exome AF: 0.366

Gnomad4 OTH exome AF: 0.390

GnomAD4 genome AF: 0.364 AC: 55255 AN: 151992 Hom.: 10889 Cov.: 32 AF XY: 0.373 AC XY: 27687 AN XY: 74290

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.778

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.361

Alfa AF: 0.362 Hom.: 24601

Bravo AF: 0.358

TwinsUK AF: 0.361 AC: 1338

ALSPAC AF: 0.369 AC: 1423

ESP6500AA AF: 0.266 AC: 1173

ESP6500EA AF: 0.362 AC: 3112

ExAC AF: 0.409 AC: 49689

Asia WGS AF: 0.587 AC: 2039 AN: 3478

EpiCase AF: 0.348

EpiControl AF: 0.349

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0027	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0000018	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.6	L
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.048
Sift	Uncertain	0.023	D
Sift4G	Benign	0.25	T
Polyphen		0.68	P
Vest4		0.19
MPC		0.11
ClinPred		0.018	T
GERP RS		3.9
Varity_R		0.086
gMVP		0.17

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: rs2070325; hg19: chr20-31673846; COSMIC: COSV64950684;