Genetic Variant BPIFB4:c.169+107T>G (chr20-33083107-T-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate

The NM_182519.3(BPIFB4):c.169+107T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0074 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0098 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BPIFB4
NM_182519.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.179

Publications

0 publications found

Variant links:

Genes affected

BPIFB4 (HGNC:16179): (BPI fold containing family B member 4) Predicted to enable lipid binding activity. Predicted to be located in cytoplasm and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

BPIFB4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 20-33083107-T-G is Benign according to our data. Variant chr20-33083107-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2652264.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BPIFB4	NM_182519.3 link	c.169+107T>G		intron_variant	Intron 4 of 17	ENST00000375483.4	NP_872325.2	P59827-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BPIFB4	ENST00000375483.4 link	c.169+107T>G		intron_variant	Intron 4 of 17	5	NM_182519.3	ENSP00000364632.3	P59827-1
BPIFB4	ENST00000674031.1 link	c.276T>G	p.Gly92Gly	synonymous_variant	Exon 2 of 15			ENSP00000501266.1	A0A669KBJ0
BPIFB4	ENST00000445356.1 link	n.106+1475T>G		intron_variant	Intron 3 of 6	2		ENSP00000388423.1	F8WEG9

Frequencies

GnomAD3 genomes

AF:

0.00745

AC:

AN:

2684

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00270

Gnomad AMI

AF:

0.0385

Gnomad AMR

AF:

0.00952

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00758

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00937

Gnomad OTH

AF:

0.0455

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00982

AC:

294

AN:

29944

Hom.:

AF XY:

0.0106

AC XY:

173

AN XY:

16318

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0103

AC:

AN:

486

American (AMR)

AF:

0.0269

AC:

AN:

1002

Ashkenazi Jewish (ASJ)

AF:

0.0163

AC:

AN:

734

East Asian (EAS)

AF:

0.00359

AC:

AN:

836

South Asian (SAS)

AF:

0.0119

AC:

AN:

5466

European-Finnish (FIN)

AF:

0.0105

AC:

AN:

2560

Middle Eastern (MID)

AF:

0.00943

AC:

AN:

106

European-Non Finnish (NFE)

AF:

0.00860

AC:

149

AN:

17324

Other (OTH)

AF:

0.00350

AC:

AN:

1430

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.289

Heterozygous variant carriers

114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00745

AC:

AN:

2686

Hom.:

Cov.:

AF XY:

0.00705

AC XY:

AN XY:

1276

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00270

AC:

AN:

740

American (AMR)

AF:

0.00952

AC:

AN:

210

Ashkenazi Jewish (ASJ)

AF:

0.0179

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

102

South Asian (SAS)

AF:

0.00

AC:

AN:

112

European-Finnish (FIN)

AF:

0.00758

AC:

AN:

132

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00937

AC:

AN:

1280

Other (OTH)

AF:

0.0417

AC:

AN:

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.283

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00194

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

BPIFB4: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

0.18

Mutation Taster

=100/0

polymorphism

(source)

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

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chr20-33083107-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over