22-32445713-GAAAAAAAAAAAA-GAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAACAAAAAAAAAAAA

Variant names:

• chr22-32445713-G-GAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAC
• rs61507713
• NM_174932.3:c.531-16_531-15insGTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_174932.3(BPIFC):​c.531-16_531-15insGTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 76,586 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 (0 hom., cov: 0)
• Consequence: BPIFC NM_174932.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980
• Publications: 0 publications found

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

ACMG classification

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.531-16_531-15insGTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT		intron	N/A	NP_777592.1	Q8NFQ6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPIFC	ENST00000300399.9	TSL:1 MANE Select	c.531-16_531-15insGTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT		intron	N/A	ENSP00000300399.3	Q8NFQ6-1
	BPIFC	ENST00000397452.5	TSL:5	c.531-16_531-15insGTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT		intron	N/A	ENSP00000380594.1	Q8NFQ6-1
	BPIFC	ENST00000534972.4	TSL:5	n.*236-16_*236-15insGTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT		intron	N/A	ENSP00000439123.3	A0A8C8NLL8

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 1 AN: 76586 Hom.: 0 Cov.: 0

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: 0.0000234

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 25

GnomAD4 genome AF: 0.0000131 AC: 1 AN: 76586 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 33648

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

African (AFR) AF: 0.00 AC: 0 AN: 20646

American (AMR) AF: 0.00 AC: 0 AN: 5022

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2324

East Asian (EAS) AF: 0.00 AC: 0 AN: 2018

South Asian (SAS) AF: 0.00 AC: 0 AN: 1554

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 694

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 76

European-Non Finnish (NFE) AF: 0.0000234 AC: 1 AN: 42672

Other (OTH) AF: 0.00 AC: 0 AN: 996

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

Other links and lift over

dbSNP: rs61507713; hg19: chr22-32841700;