20-33291009-A-G

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.418A>G(p.Thr140Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00287 in 1,613,926 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.015 (56 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (53 hom.)
• Consequence: BPIFB1 NM_033197.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.246

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=0.0040444434).
• BP6: Variant 20-33291009-A-G is Benign according to our data. Variant chr20-33291009-A-G is described in ClinVar as [Benign]. Clinvar id is 775647.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0146 (2217/152264) while in subpopulation AFR AF= 0.0492 (2044/41552). AF 95% confidence interval is 0.0474. There are 56 homozygotes in gnomad4. There are 1087 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 57 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BPIFB1	NM_033197.3	c.418A>G	p.Thr140Ala	missense_variant	5/16	ENST00000253354.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BPIFB1	ENST00000253354.2	c.418A>G	p.Thr140Ala	missense_variant	5/16	1	NM_033197.3	P1
BPIFB1	ENST00000423645.5	c.418A>G	p.Thr140Ala	missense_variant	5/5	3

Frequencies

GnomAD3 genomes AF: 0.0145 AC: 2210 AN: 152146 Hom.: 57 Cov.: 33

Gnomad AFR AF: 0.0492

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.00370 AC: 927 AN: 250832 Hom.: 20 AF XY: 0.00285 AC XY: 386 AN XY: 135652

Gnomad AFR exome AF: 0.0484

Gnomad AMR exome AF: 0.00220

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000335

Gnomad OTH exome AF: 0.00311

GnomAD4 exome AF: 0.00166 AC: 2421 AN: 1461662 Hom.: 53 Cov.: 31 AF XY: 0.00146 AC XY: 1060 AN XY: 727146

Gnomad4 AFR exome AF: 0.0513

Gnomad4 AMR exome AF: 0.00273

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000220

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000237

Gnomad4 OTH exome AF: 0.00427

GnomAD4 genome AF: 0.0146 AC: 2217 AN: 152264 Hom.: 56 Cov.: 33 AF XY: 0.0146 AC XY: 1087 AN XY: 74446

Gnomad4 AFR AF: 0.0492

Gnomad4 AMR AF: 0.00758

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000382

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.00171 Hom.: 9

Bravo AF: 0.0169

ESP6500AA AF: 0.0374 AC: 165

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.00434 AC: 527

Asia WGS AF: 0.00289 AC: 11 AN: 3478

EpiCase AF: 0.000491

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

Feb 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.60
Cadd	Benign	0.16
Dann	Benign	0.41
DEOGEN2	Benign	0.0054	T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.35	T;T
MetaRNN	Benign	0.0040	T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.10	N;N
REVEL	Benign	0.049
Sift	Uncertain	0.015	D;T
Sift4G	Uncertain	0.016	D;D
Polyphen		0.0	.;B
Vest4		0.21
MVP		0.014
MPC		0.17
ClinPred		0.0068	T
GERP RS		-4.7
Varity_R		0.027
gMVP		0.095

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: rs34578060; hg19: chr20-31878815; COSMIC: COSV99037080;