rs2093066

Positions:

• chr20-33064790-C-T

Variant summary

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

The ENST00000375494.4(BPIFB3):​c.857C>T​(p.Thr286Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,613,842 control chromosomes in the GnomAD database, including 16,593 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.14 (1785 hom., cov: 31)
  • Exomes 𝑓: 0.14 (14808 hom.)
• Consequence: BPIFB3 ENST00000375494.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03

Genes affected

BPIFB3 (HGNC:16178): (BPI fold containing family B member 3) Predicted to enable lipid binding activity. Located in cytoplasm. [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=0.0036616623).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPIFB3	NM_001376932.3	c.857C>T	p.Thr286Met	missense_variant	9/16	ENST00000375494.4	NP_001363861.2
BPIFB3	NM_182658.5	c.857C>T	p.Thr286Met	missense_variant	8/15		NP_872599.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BPIFB3	ENST00000375494.4	c.857C>T	p.Thr286Met	missense_variant	9/16	1	NM_001376932.3	ENSP00000364643	P1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21877 AN: 151992 Hom.: 1776 Cov.: 31

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0874

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0483

Gnomad SAS AF: 0.0606

Gnomad FIN AF: 0.0678

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.151

GnomAD3 exomes AF: 0.113 AC: 28419 AN: 251200 Hom.: 1878 AF XY: 0.112 AC XY: 15168 AN XY: 135778

Gnomad AFR exome AF: 0.213

Gnomad AMR exome AF: 0.0629

Gnomad ASJ exome AF: 0.167

Gnomad EAS exome AF: 0.0504

Gnomad SAS exome AF: 0.0730

Gnomad FIN exome AF: 0.0712

Gnomad NFE exome AF: 0.138

Gnomad OTH exome AF: 0.123

GnomAD4 exome AF: 0.137 AC: 199924 AN: 1461732 Hom.: 14808 Cov.: 35 AF XY: 0.134 AC XY: 97675 AN XY: 727184

Gnomad4 AFR exome AF: 0.221

Gnomad4 AMR exome AF: 0.0673

Gnomad4 ASJ exome AF: 0.169

Gnomad4 EAS exome AF: 0.0465

Gnomad4 SAS exome AF: 0.0739

Gnomad4 FIN exome AF: 0.0689

Gnomad4 NFE exome AF: 0.148

Gnomad4 OTH exome AF: 0.135

GnomAD4 genome AF: 0.144 AC: 21896 AN: 152110 Hom.: 1785 Cov.: 31 AF XY: 0.136 AC XY: 10096 AN XY: 74378

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.0873

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.0483

Gnomad4 SAS AF: 0.0600

Gnomad4 FIN AF: 0.0678

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.154

Alfa AF: 0.140 Hom.: 3844

Bravo AF: 0.151

TwinsUK AF: 0.145 AC: 536

ALSPAC AF: 0.149 AC: 574

ESP6500AA AF: 0.204 AC: 900

ESP6500EA AF: 0.145 AC: 1249

ExAC AF: 0.115 AC: 13973

Asia WGS AF: 0.0790 AC: 273 AN: 3478

EpiCase AF: 0.145

EpiControl AF: 0.143

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.15	T
MetaRNN	Benign	0.0037	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.69	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.061
Sift	Benign	0.10	T
Sift4G	Uncertain	0.0090	D
Polyphen		0.0	B
Vest4		0.050
MPC		0.095
ClinPred		0.023	T
GERP RS		4.7
Varity_R		0.029
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2093066; hg19: chr20-31652596;