Genetic Variant BPIFC:c.531-17_531-16delTT (chr22-32445713-GAA-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_174932.3(BPIFC):c.531-17_531-16delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00865 in 707,696 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 0)

Exomes 𝑓: 0.0095 ( 0 hom. )

Consequence

BPIFC
NM_174932.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.218

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: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00197 (151/76600) while in subpopulation SAS AF = 0.0408 (63/1544). AF 95% confidence interval is 0.0327. There are 1 homozygotes in GnomAd4. There are 82 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High AC in GnomAd4 at 151 AD gene.

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.531-17_531-16delTT		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.531-17_531-16delTT	intron	N/A	ENSP00000300399.3	Q8NFQ6-1
BPIFC	ENST00000397452.5	TSL:5	c.531-17_531-16delTT	intron	N/A	ENSP00000380594.1	Q8NFQ6-1
BPIFC	ENST00000534972.4	TSL:5	n.236-17_236-16delTT	intron	N/A	ENSP00000439123.3	A0A8C8NLL8

Frequencies

GnomAD3 genomes

AF:

0.00197

AC:

151

AN:

76586

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00387

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000398

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000496

Gnomad SAS

AF:

0.0405

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000117

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00946

AC:

5969

AN:

631096

Hom.:

AF XY:

0.0101

AC XY:

3209

AN XY:

318868

show subpopulations

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

African (AFR)

AF:

0.00727

AC:

119

AN:

16366

American (AMR)

AF:

0.00770

AC:

112

AN:

14544

Ashkenazi Jewish (ASJ)

AF:

0.00621

AC:

AN:

11592

East Asian (EAS)

AF:

0.00718

AC:

170

AN:

23678

South Asian (SAS)

AF:

0.0233

AC:

906

AN:

38818

European-Finnish (FIN)

AF:

0.0114

AC:

254

AN:

22254

Middle Eastern (MID)

AF:

0.00256

AC:

AN:

1956

European-Non Finnish (NFE)

AF:

0.00850

AC:

4027

AN:

474018

Other (OTH)

AF:

0.0109

AC:

304

AN:

27870

⚠️ 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: 0.306

Heterozygous variant carriers

435

869

1304

1738

2173

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

124

248

372

496

620

<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:

0.00197

AC:

151

AN:

76600

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

AN XY:

33662

show subpopulations

African (AFR)

AF:

0.00387

AC:

AN:

20668

American (AMR)

AF:

0.000398

AC:

AN:

5028

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2324

East Asian (EAS)

AF:

0.000497

AC:

AN:

2014

South Asian (SAS)

AF:

0.0408

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:

0.000117

AC:

AN:

42670

Other (OTH)

AF:

0.00

AC:

AN:

998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

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

Alfa

AF:

0.00

Hom.:

131

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.22

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

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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