Genetic Variant BPIFC:c.531-16delT (chr22-32445713-GA-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.531-16delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.052 in 706,008 control chromosomes in the GnomAD database, including 35 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.028 ( 14 hom., cov: 0)

Exomes 𝑓: 0.055 ( 21 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: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0277 (2122/76530) while in subpopulation NFE AF = 0.031 (1324/42642). AF 95% confidence interval is 0.0297. There are 14 homozygotes in GnomAd4. There are 918 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High AC in GnomAd4 at 2122 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.531-16delT		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.531-16delT	intron	N/A	ENSP00000300399.3	Q8NFQ6-1
BPIFC	ENST00000397452.5	TSL:5	c.531-16delT	intron	N/A	ENSP00000380594.1	Q8NFQ6-1
BPIFC	ENST00000534972.4	TSL:5	n.*236-16delT	intron	N/A	ENSP00000439123.3	A0A8C8NLL8

Frequencies

GnomAD3 genomes

AF:

0.0278

AC:

2124

AN:

76516

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0307

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0229

Gnomad ASJ

AF:

0.00474

Gnomad EAS

AF:

0.000496

Gnomad SAS

AF:

0.00772

Gnomad FIN

AF:

0.0187

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0310

Gnomad OTH

AF:

0.0161

GnomAD4 exome

AF:

0.0549

AC:

34583

AN:

629478

Hom.:

Cov.:

AF XY:

0.0544

AC XY:

17321

AN XY:

318122

show subpopulations

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

African (AFR)

AF:

0.0362

AC:

589

AN:

16292

American (AMR)

AF:

0.0329

AC:

477

AN:

14508

Ashkenazi Jewish (ASJ)

AF:

0.0283

AC:

327

AN:

11550

East Asian (EAS)

AF:

0.0388

AC:

916

AN:

23592

South Asian (SAS)

AF:

0.0297

AC:

1153

AN:

38782

European-Finnish (FIN)

AF:

0.0559

AC:

1237

AN:

22144

Middle Eastern (MID)

AF:

0.0419

AC:

AN:

1958

European-Non Finnish (NFE)

AF:

0.0600

AC:

28393

AN:

472854

Other (OTH)

AF:

0.0507

AC:

1409

AN:

27798

⚠️ 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: 0.376

Heterozygous variant carriers

1739

3478

5218

6957

8696

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

954

1908

2862

3816

4770

<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:

0.0277

AC:

2122

AN:

76530

Hom.:

Cov.:

AF XY:

0.0273

AC XY:

918

AN XY:

33640

show subpopulations

African (AFR)

AF:

0.0306

AC:

631

AN:

20630

American (AMR)

AF:

0.0227

AC:

114

AN:

5028

Ashkenazi Jewish (ASJ)

AF:

0.00474

AC:

AN:

2320

East Asian (EAS)

AF:

0.000497

AC:

AN:

2014

South Asian (SAS)

AF:

0.00777

AC:

AN:

1544

European-Finnish (FIN)

AF:

0.0187

AC:

AN:

694

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0310

AC:

1324

AN:

42642

Other (OTH)

AF:

0.0160

AC:

AN:

998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

149

223

298

372

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0182

Hom.:

131

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.098

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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22-32445713-GAAAAAAAAAAAA-GAAAAAAAAAAA

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