rs378098

Positions:

• chr20-33072737-C-T

Variant summary

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

The NM_001376932.3(BPIFB3):​c.1333C>T​(p.Pro445Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,611,942 control chromosomes in the GnomAD database, including 17,812 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.16 (2273 hom., cov: 32)
  • Exomes 𝑓: 0.14 (15539 hom.)
• Consequence: BPIFB3 NM_001376932.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.31

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=0.0022091866).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPIFB3	NM_001376932.3	c.1333C>T	p.Pro445Ser	missense_variant	15/16	ENST00000375494.4	NP_001363861.2
BPIFB3	NM_182658.5	c.1333C>T	p.Pro445Ser	missense_variant	14/15		NP_872599.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BPIFB3	ENST00000375494.4	c.1333C>T	p.Pro445Ser	missense_variant	15/16	1	NM_001376932.3	ENSP00000364643	P1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24100 AN: 151994 Hom.: 2264 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.0584

Gnomad AMR AF: 0.0954

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0485

Gnomad SAS AF: 0.0623

Gnomad FIN AF: 0.0697

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.169

GnomAD3 exomes AF: 0.118 AC: 29738 AN: 251438 Hom.: 2134 AF XY: 0.116 AC XY: 15778 AN XY: 135902

Gnomad AFR exome AF: 0.259

Gnomad AMR exome AF: 0.0673

Gnomad ASJ exome AF: 0.169

Gnomad EAS exome AF: 0.0505

Gnomad SAS exome AF: 0.0744

Gnomad FIN exome AF: 0.0745

Gnomad NFE exome AF: 0.140

Gnomad OTH exome AF: 0.126

GnomAD4 exome AF: 0.139 AC: 203410 AN: 1459830 Hom.: 15539 Cov.: 32 AF XY: 0.137 AC XY: 99405 AN XY: 726420

Gnomad4 AFR exome AF: 0.268

Gnomad4 AMR exome AF: 0.0719

Gnomad4 ASJ exome AF: 0.169

Gnomad4 EAS exome AF: 0.0464

Gnomad4 SAS exome AF: 0.0754

Gnomad4 FIN exome AF: 0.0716

Gnomad4 NFE exome AF: 0.149

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome AF: 0.159 AC: 24117 AN: 152112 Hom.: 2273 Cov.: 32 AF XY: 0.150 AC XY: 11159 AN XY: 74380

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.0953

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.0484

Gnomad4 SAS AF: 0.0620

Gnomad4 FIN AF: 0.0697

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.171

Alfa AF: 0.145 Hom.: 4163

Bravo AF: 0.168

TwinsUK AF: 0.147 AC: 546

ALSPAC AF: 0.152 AC: 585

ESP6500AA AF: 0.243 AC: 1070

ESP6500EA AF: 0.147 AC: 1261

ExAC AF: 0.121 AC: 14686

Asia WGS AF: 0.0770 AC: 267 AN: 3478

EpiCase AF: 0.147

EpiControl AF: 0.145

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.63	T
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
MutationTaster	Benign	0.0030	P
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.26
MPC		0.49
ClinPred		0.017	T
GERP RS		4.6
Varity_R		0.79
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs378098; hg19: chr20-31660543;