20-33011102-C-T

Variant names:

• chr20-33011102-C-T
• rs34128772
• NM_025227.3:c.188C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_025227.3(BPIFB2):​c.188C>T​(p.Ala63Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00157 in 1,613,674 control chromosomes in the GnomAD database, including 41 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 the same amino acid substitution has been previously reported as Likely benign in UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A63E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0083 (18 hom., cov: 32)
  • Exomes 𝑓: 0.00087 (23 hom.)
• Consequence: BPIFB2 NM_025227.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

Genes affected

BPIFB2 (HGNC:16177): (BPI fold containing family B member 2) This gene encodes a member of the lipid transfer/lipopolysaccharide binding protein (LT/LBP) gene family. It is highly expressed in hypertrophic tonsils. This gene and three other members of the LT/LBP gene family form a cluster on the long arm of chromosome 20. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015248954).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0083 (1263/152246) while in subpopulation AFR AF= 0.0285 (1185/41554). AF 95% confidence interval is 0.0272. There are 18 homozygotes in gnomad4. There are 627 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BPIFB2	NM_025227.3	c.188C>T	p.Ala63Val	missense_variant	Exon 3 of 16	ENST00000170150.4	NP_079503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BPIFB2	ENST00000170150.4	c.188C>T	p.Ala63Val	missense_variant	Exon 3 of 16	1	NM_025227.3	ENSP00000170150.3

Frequencies

GnomAD3 genomes AF: 0.00828 AC: 1260 AN: 152128 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.0285

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00380

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00223 AC: 561 AN: 251148 Hom.: 4 AF XY: 0.00157 AC XY: 213 AN XY: 135736

Gnomad AFR exome AF: 0.0308

Gnomad AMR exome AF: 0.00131

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.0000981

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000872 AC: 1275 AN: 1461428 Hom.: 23 Cov.: 31 AF XY: 0.000744 AC XY: 541 AN XY: 727058

Gnomad4 AFR exome AF: 0.0305

Gnomad4 AMR exome AF: 0.00161

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000540

Gnomad4 OTH exome AF: 0.00184

GnomAD4 genome AF: 0.00830 AC: 1263 AN: 152246 Hom.: 18 Cov.: 32 AF XY: 0.00842 AC XY: 627 AN XY: 74440

Gnomad4 AFR AF: 0.0285

Gnomad4 AMR AF: 0.00379

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00143 Hom.: 4

Bravo AF: 0.00949

ESP6500AA AF: 0.0275 AC: 121

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00290 AC: 352

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.77
DANN	Benign	0.83
DEOGEN2	Benign	0.0035	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0052	N
LIST_S2	Benign	0.14	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.8	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.18	N
REVEL	Benign	0.012
Sift	Benign	0.32	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.12
MVP		0.014
MPC		0.17
ClinPred		0.0012	T
GERP RS		-5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.032
gMVP		0.094

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs34128772; hg19: chr20-31598908;