22-32445713-GAAAAAAAAAAAA-GAAAAAAAAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr22-32445713-G-GAAAAAAAAAAAAAAAA
• rs61507713
• NM_174932.3:c.531-31_531-16dupTTTTTTTTTTTTTTTT

Variant summary

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

The NM_174932.3(BPIFC):​c.531-31_531-16dupTTTTTTTTTTTTTTTT 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. There is a variant allele frequency bias in the population database for this variant (GnomAd4), 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 0.00013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00052 (3 hom.)
  • Failed GnomAD Quality Control
• 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.531-31_531-16dupTTTTTTTTTTTTTTTT		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_531-15insTTTTTTTTTTTTTTTT		intron	N/A	ENSP00000300399.3	Q8NFQ6-1
	BPIFC	ENST00000397452.5	TSL:5	c.531-16_531-15insTTTTTTTTTTTTTTTT		intron	N/A	ENSP00000380594.1	Q8NFQ6-1
	BPIFC	ENST00000534972.4	TSL:5	n.*236-16_*236-15insTTTTTTTTTTTTTTTT		intron	N/A	ENSP00000439123.3	A0A8C8NLL8

Frequencies

GnomAD3 genomes AF: 0.000131 AC: 10 AN: 76576 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000969

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000861

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000141

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000519 AC: 329 AN: 634318 Hom.: 3 Cov.: 25 AF XY: 0.000586 AC XY: 188 AN XY: 320590

African (AFR) AF: 0.000183 AC: 3 AN: 16406

American (AMR) AF: 0.000958 AC: 14 AN: 14612

Ashkenazi Jewish (ASJ) AF: 0.000515 AC: 6 AN: 11642

East Asian (EAS) AF: 0.00101 AC: 24 AN: 23822

South Asian (SAS) AF: 0.00255 AC: 100 AN: 39142

European-Finnish (FIN) AF: 0.000402 AC: 9 AN: 22408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1962

European-Non Finnish (NFE) AF: 0.000342 AC: 163 AN: 476294

Other (OTH) AF: 0.000357 AC: 10 AN: 28030

GnomAD4 genome AF: 0.000131 AC: 10 AN: 76590 Hom.: 0 Cov.: 0 AF XY: 0.000119 AC XY: 4 AN XY: 33660

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

African (AFR) AF: 0.0000968 AC: 2 AN: 20668

American (AMR) AF: 0.00 AC: 0 AN: 5026

Ashkenazi Jewish (ASJ) AF: 0.000861 AC: 2 AN: 2322

East Asian (EAS) AF: 0.00 AC: 0 AN: 2014

South Asian (SAS) AF: 0.00 AC: 0 AN: 1544

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: 0.000141 AC: 6 AN: 42664

Other (OTH) AF: 0.00 AC: 0 AN: 998

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000000549349), 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;