Genetic Variant BPIFC:c.531-30_531-16dupTTTTTTTTTTTTTTT (chr22-32445713-G-GAAAAAAAAAAAAAAA) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_174932.3(BPIFC):c.531-30_531-16dupTTTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00086 ( 3 hom. )

Failed GnomAD Quality Control

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BS2

High AC in GnomAd4 at 23 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.531-30_531-16dupTTTTTTTTTTTTTTT		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_531-15insTTTTTTTTTTTTTTT	intron	N/A	ENSP00000300399.3	Q8NFQ6-1
BPIFC	ENST00000397452.5	TSL:5	c.531-16_531-15insTTTTTTTTTTTTTTT	intron	N/A	ENSP00000380594.1	Q8NFQ6-1
BPIFC	ENST00000534972.4	TSL:5	n.236-16_236-15insTTTTTTTTTTTTTTT	intron	N/A	ENSP00000439123.3	A0A8C8NLL8

Frequencies

GnomAD3 genomes

AF:

0.000300

AC:

AN:

76540

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000339

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000598

Gnomad ASJ

AF:

0.000431

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000258

Gnomad OTH

AF:

0.00101

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000864

AC:

548

AN:

633962

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

347

AN XY:

320408

show subpopulations

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

African (AFR)

AF:

0.000610

AC:

AN:

16406

American (AMR)

AF:

0.00213

AC:

AN:

14586

Ashkenazi Jewish (ASJ)

AF:

0.00121

AC:

AN:

11618

East Asian (EAS)

AF:

0.00126

AC:

AN:

23812

South Asian (SAS)

AF:

0.00379

AC:

148

AN:

39080

European-Finnish (FIN)

AF:

0.00120

AC:

AN:

22408

Middle Eastern (MID)

AF:

0.000510

AC:

AN:

1960

European-Non Finnish (NFE)

AF:

0.000548

AC:

261

AN:

476088

Other (OTH)

AF:

0.000928

AC:

AN:

28004

⚠️ 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: 0.398

Heterozygous variant carriers

112

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:

0.000300

AC:

AN:

76554

Hom.:

Cov.:

AF XY:

0.000297

AC XY:

AN XY:

33646

show subpopulations

African (AFR)

AF:

0.000339

AC:

AN:

20656

American (AMR)

AF:

0.000597

AC:

AN:

5024

Ashkenazi Jewish (ASJ)

AF:

0.000431

AC:

AN:

2320

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:

0.000258

AC:

AN:

42646

Other (OTH)

AF:

0.00100

AC:

AN:

996

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.412

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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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