20-33289964-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_033197.3(BPIFB1):c.337C>T(p.Pro113Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00186 in 1,614,148 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0097 (26 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (28 hom.)
• Consequence: BPIFB1 NM_033197.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.49

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008732051).
• BP6: Variant 20-33289964-C-T is Benign according to our data. Variant chr20-33289964-C-T is described in ClinVar as [Benign]. Clinvar id is 714898.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00971 (1479/152272) while in subpopulation AFR AF= 0.0339 (1407/41536). AF 95% confidence interval is 0.0324. There are 26 homozygotes in gnomad4. There are 721 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BPIFB1	NM_033197.3	c.337C>T	p.Pro113Ser	missense_variant	4/16	ENST00000253354.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BPIFB1	ENST00000253354.2	c.337C>T	p.Pro113Ser	missense_variant	4/16	1	NM_033197.3	P1
BPIFB1	ENST00000423645.5	c.337C>T	p.Pro113Ser	missense_variant	4/5	3

Frequencies

GnomAD3 genomes AF: 0.00969 AC: 1474 AN: 152154 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.0338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00282

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00766

GnomAD3 exomes AF: 0.00268 AC: 674 AN: 251456 Hom.: 13 AF XY: 0.00191 AC XY: 260 AN XY: 135916

Gnomad AFR exome AF: 0.0355

Gnomad AMR exome AF: 0.00208

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00104 AC: 1526 AN: 1461876 Hom.: 28 Cov.: 31 AF XY: 0.000903 AC XY: 657 AN XY: 727238

Gnomad4 AFR exome AF: 0.0352

Gnomad4 AMR exome AF: 0.00224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000818

Gnomad4 OTH exome AF: 0.00228

GnomAD4 genome AF: 0.00971 AC: 1479 AN: 152272 Hom.: 26 Cov.: 32 AF XY: 0.00968 AC XY: 721 AN XY: 74452

Gnomad4 AFR AF: 0.0339

Gnomad4 AMR AF: 0.00281

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.00144 Hom.: 3

Bravo AF: 0.0111

ESP6500AA AF: 0.0386 AC: 170

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00320 AC: 388

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 15, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.45
Cadd	Uncertain	24
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.082	T;T
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.81	T;T
MetaRNN	Benign	0.0087	T;T
MetaSVM	Benign	-1.2	T
MutationTaster	Benign	0.97	D
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-8.0	D;D
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.73
MVP		0.54
MPC		0.70
ClinPred		0.061	T
GERP RS		5.4
Varity_R		0.82
gMVP		0.50

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: rs114635109; hg19: chr20-31877770;