Genetic Variant BPIFC:c.531-22_531-16dupTTTTTTT (chr22-32445713-G-GAAAAAAA) – 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.531-22_531-16dupTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 710,686 control chromosomes in the GnomAD database, including 28 homozygotes. 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 0.000052 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0012 ( 28 hom. )

Consequence

BPIFC
NM_174932.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0980

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:

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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.531-22_531-16dupTTTTTTT		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.531-16_531-15insTTTTTTT	intron	N/A	ENSP00000300399.3	Q8NFQ6-1
BPIFC	ENST00000397452.5	TSL:5	c.531-16_531-15insTTTTTTT	intron	N/A	ENSP00000380594.1	Q8NFQ6-1
BPIFC	ENST00000534972.4	TSL:5	n.236-16_236-15insTTTTTTT	intron	N/A	ENSP00000439123.3	A0A8C8NLL8

Frequencies

GnomAD3 genomes

AF:

0.0000522

AC:

AN:

76586

Hom.:

Cov.:

show subpopulations

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:

0.0000937

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00118

AC:

751

AN:

634086

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

440

AN XY:

320470

show subpopulations

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

African (AFR)

AF:

0.000915

AC:

AN:

16388

American (AMR)

AF:

0.00357

AC:

AN:

14582

Ashkenazi Jewish (ASJ)

AF:

0.00163

AC:

AN:

11630

East Asian (EAS)

AF:

0.00189

AC:

AN:

23784

South Asian (SAS)

AF:

0.00488

AC:

191

AN:

39118

European-Finnish (FIN)

AF:

0.00170

AC:

AN:

22410

Middle Eastern (MID)

AF:

0.00153

AC:

AN:

1966

European-Non Finnish (NFE)

AF:

0.000739

AC:

352

AN:

476186

Other (OTH)

AF:

0.00128

AC:

AN:

28022

⚠️ 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: 0.387

Heterozygous variant carriers

125

156

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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

AF:

0.0000522

AC:

AN:

76600

Hom.:

Cov.:

AF XY:

0.0000594

AC XY:

AN XY:

33664

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20668

American (AMR)

AF:

0.00

AC:

AN:

5028

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2324

East Asian (EAS)

AF:

0.00

AC:

AN:

2014

South Asian (SAS)

AF:

0.00

AC:

AN:

1544

European-Finnish (FIN)

AF:

0.00

AC:

AN:

694

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0000937

AC:

AN:

42670

Other (OTH)

AF:

0.00

AC:

AN:

998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.098

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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22-32445713-GAAAAAAAAAAAA-GAAAAAAAAAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over