Genetic Variant BPIFC:c.531-19_531-16dupTTTT (chr22-32445713-G-GAAAA) – 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.531-19_531-16dupTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0339 in 624,232 control chromosomes in the GnomAD database, including 397 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 0.015 ( 33 hom., cov: 0)

Exomes 𝑓: 0.034 ( 397 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:

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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.531-19_531-16dupTTTT		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_531-15insTTTT	intron	N/A	ENSP00000300399.3	Q8NFQ6-1
BPIFC	ENST00000397452.5	TSL:5	c.531-16_531-15insTTTT	intron	N/A	ENSP00000380594.1	Q8NFQ6-1
BPIFC	ENST00000534972.4	TSL:5	n.236-16_236-15insTTTT	intron	N/A	ENSP00000439123.3	A0A8C8NLL8

Frequencies

GnomAD3 genomes

AF:

0.0148

AC:

1134

AN:

76434

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0158

Gnomad AMI

AF:

0.0120

Gnomad AMR

AF:

0.00918

Gnomad ASJ

AF:

0.0211

Gnomad EAS

AF:

0.0283

Gnomad SAS

AF:

0.0174

Gnomad FIN

AF:

0.0159

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0140

Gnomad OTH

AF:

0.0131

GnomAD4 exome

AF:

0.0339

AC:

21169

AN:

624232

Hom.:

397

Cov.:

AF XY:

0.0352

AC XY:

11095

AN XY:

315454

show subpopulations

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

African (AFR)

AF:

0.0247

AC:

397

AN:

16052

American (AMR)

AF:

0.0516

AC:

729

AN:

14134

Ashkenazi Jewish (ASJ)

AF:

0.0410

AC:

467

AN:

11392

East Asian (EAS)

AF:

0.0414

AC:

955

AN:

23090

South Asian (SAS)

AF:

0.0684

AC:

2624

AN:

38342

European-Finnish (FIN)

AF:

0.0411

AC:

899

AN:

21898

Middle Eastern (MID)

AF:

0.0292

AC:

AN:

1918

European-Non Finnish (NFE)

AF:

0.0300

AC:

14084

AN:

469934

Other (OTH)

AF:

0.0349

AC:

958

AN:

27472

⚠️ 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: 0.370

Heterozygous variant carriers

1109

2219

3328

4438

5547

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

432

864

1296

1728

2160

<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: AS_VQSR

AF:

0.0148

AC:

1134

AN:

76448

Hom.:

Cov.:

AF XY:

0.0149

AC XY:

501

AN XY:

33596

show subpopulations

African (AFR)

AF:

0.0158

AC:

326

AN:

20616

American (AMR)

AF:

0.00917

AC:

AN:

5018

Ashkenazi Jewish (ASJ)

AF:

0.0211

AC:

AN:

2318

East Asian (EAS)

AF:

0.0284

AC:

AN:

2008

South Asian (SAS)

AF:

0.0175

AC:

AN:

1540

European-Finnish (FIN)

AF:

0.0159

AC:

AN:

692

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0140

AC:

598

AN:

42600

Other (OTH)

AF:

0.0130

AC:

AN:

998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.433

Heterozygous variant carriers

102

136

170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.0282

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

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

Publications

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22-32445713-GAAAAAAAAAAAA-GAAAAAAAAAAAAAAAA

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