Genetic Variant BPIFC:c.531-18_531-16delTTT (chr22-32445713-GAAA-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_174932.3(BPIFC):c.531-18_531-16delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 633,380 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0017 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BPIFC
NM_174932.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.416

Publications

0 publications found

Variant links:

Genes affected

BPIFC (HGNC:16503): (BPI fold containing family C) Predicted to enable lipid binding activity. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

BPIFC Gene-Disease associations (from GenCC):

trichilemmal cyst
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

BPIFC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174932.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPIFC	NM_174932.3	MANE Select	c.531-18_531-16delTTT		intron	N/A	NP_777592.1	Q8NFQ6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BPIFC	ENST00000300399.9	TSL:1 MANE Select	c.531-18_531-16delTTT	intron	N/A	ENSP00000300399.3	Q8NFQ6-1
BPIFC	ENST00000397452.5	TSL:5	c.531-18_531-16delTTT	intron	N/A	ENSP00000380594.1	Q8NFQ6-1
BPIFC	ENST00000534972.4	TSL:5	n.236-18_236-16delTTT	intron	N/A	ENSP00000439123.3	A0A8C8NLL8

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

76586

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00167

AC:

1060

AN:

633380

Hom.:

AF XY:

0.00183

AC XY:

587

AN XY:

320150

show subpopulations

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

African (AFR)

AF:

0.00146

AC:

AN:

16396

American (AMR)

AF:

0.00219

AC:

AN:

14586

Ashkenazi Jewish (ASJ)

AF:

0.00129

AC:

AN:

11612

East Asian (EAS)

AF:

0.00189

AC:

AN:

23754

South Asian (SAS)

AF:

0.00429

AC:

168

AN:

39160

European-Finnish (FIN)

AF:

0.00291

AC:

AN:

22338

Middle Eastern (MID)

AF:

0.000510

AC:

AN:

1962

European-Non Finnish (NFE)

AF:

0.00141

AC:

669

AN:

475586

Other (OTH)

AF:

0.00147

AC:

AN:

27986

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.286

Heterozygous variant carriers

188

283

377

471

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

76586

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33648

African (AFR)

AF:

0.00

AC:

AN:

20646

American (AMR)

AF:

0.00

AC:

AN:

5022

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2324

East Asian (EAS)

AF:

0.00

AC:

AN:

2018

South Asian (SAS)

AF:

0.00

AC:

AN:

1554

European-Finnish (FIN)

AF:

0.00

AC:

AN:

694

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

42672

Other (OTH)

AF:

0.00

AC:

AN:

996

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.42

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

22-32445713-GAAAAAAAAAAAA-GAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over