Variant chr20-33288741-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_033197.3(BPIFB1):c.116A>G(p.Lys39Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,613,412 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 19 hom., cov: 33)

Exomes 𝑓: 0.00075 ( 17 hom. )

Consequence

BPIFB1
NM_033197.3 missense, splice_region

Scores

Splicing: ADA: 0.00005259

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.756

Variant links:

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]

BPIFB1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028855205).

BP6

Variant 20-33288741-A-G is Benign according to our data. Variant chr20-33288741-A-G is described in ClinVar as [Benign]. Clinvar id is 780603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00764 (1163/152234) while in subpopulation AFR AF= 0.0262 (1090/41550). AF 95% confidence interval is 0.0249. There are 19 homozygotes in gnomad4. There are 590 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BPIFB1	NM_033197.3 linkuse as main transcript	c.116A>G	p.Lys39Arg	missense_variant, splice_region_variant	3/16	ENST00000253354.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BPIFB1	ENST00000253354.2 linkuse as main transcript	c.116A>G	p.Lys39Arg	missense_variant, splice_region_variant	3/16	1	NM_033197.3	P1	Q8TDL5-1
BPIFB1	ENST00000423645.5 linkuse as main transcript	c.116A>G	p.Lys39Arg	missense_variant, splice_region_variant	3/5	3

Frequencies

GnomAD3 genomes

AF:

0.00765

AC:

1163

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0263

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00367

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00198

AC:

492

AN:

248018

Hom.:

AF XY:

0.00159

AC XY:

214

AN XY:

134398

show subpopulations

Gnomad AFR exome

AF:

0.0250

Gnomad AMR exome

AF:

0.00215

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:

0.0000632

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.000749

AC:

1095

AN:

1461178

Hom.:

Cov.:

AF XY:

0.000667

AC XY:

485

AN XY:

726860

show subpopulations

Gnomad4 AFR exome

AF:

0.0243

Gnomad4 AMR exome

AF:

0.00195

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000648

Gnomad4 OTH exome

AF:

0.00199

GnomAD4 genome

AF:

0.00764

AC:

1163

AN:

152234

Hom.:

Cov.:

AF XY:

0.00793

AC XY:

590

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0262

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00170

Hom.:

Bravo

AF:

0.00858

ESP6500AA

AF:

0.0245

AC:

108

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00254

AC:

309

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.65

CADD

Benign

1.8

DANN

Benign

0.73

DEOGEN2

Benign

0.024

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.53

T;T

MetaRNN

Benign

0.0029

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

.;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.99

N;N

REVEL

Benign

0.050

Sift

Benign

0.61

T;T

Sift4G

Benign

0.47

T;T

Polyphen

0.0010

.;B

Vest4

0.040

MVP

0.085

MPC

0.14

ClinPred

0.0091

GERP RS

-10

Varity_R

0.027

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000053

dbscSNV1_RF

Benign

0.064

SpliceAI score (max)

0.080

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over