22-32445713-GAAAAAAAAAAAA-GAAAAAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr22-32445713-G-GAAAAAAAAAAAAA
• rs61507713
• NM_174932.3:c.531-28_531-16dupTTTTTTTTTTTTT

Variant summary

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

The NM_174932.3(BPIFC):​c.531-28_531-16dupTTTTTTTTTTTTT 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 0.0019 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0029 (19 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.531-28_531-16dupTTTTTTTTTTTTT		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_531-15insTTTTTTTTTTTTT		intron	N/A	ENSP00000300399.3	Q8NFQ6-1
	BPIFC	ENST00000397452.5	TSL:5	c.531-16_531-15insTTTTTTTTTTTTT		intron	N/A	ENSP00000380594.1	Q8NFQ6-1
	BPIFC	ENST00000534972.4	TSL:5	n.*236-16_*236-15insTTTTTTTTTTTTT		intron	N/A	ENSP00000439123.3	A0A8C8NLL8

Frequencies

GnomAD3 genomes AF: 0.00186 AC: 142 AN: 76304 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00126

Gnomad AMI AF: 0.00515

Gnomad AMR AF: 0.00200

Gnomad ASJ AF: 0.000867

Gnomad EAS AF: 0.00249

Gnomad SAS AF: 0.00129

Gnomad FIN AF: 0.00145

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00219

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00290 AC: 1835 AN: 632562 Hom.: 19 Cov.: 25 AF XY: 0.00344 AC XY: 1100 AN XY: 319550

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

African (AFR) AF: 0.00165 AC: 27 AN: 16358

American (AMR) AF: 0.00730 AC: 106 AN: 14518

Ashkenazi Jewish (ASJ) AF: 0.00414 AC: 48 AN: 11608

East Asian (EAS) AF: 0.00324 AC: 77 AN: 23760

South Asian (SAS) AF: 0.0112 AC: 433 AN: 38830

European-Finnish (FIN) AF: 0.00354 AC: 79 AN: 22344

Middle Eastern (MID) AF: 0.00357 AC: 7 AN: 1962

European-Non Finnish (NFE) AF: 0.00207 AC: 985 AN: 475242

Other (OTH) AF: 0.00261 AC: 73 AN: 27940

⚠️ 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.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00186 AC: 142 AN: 76318 Hom.: 1 Cov.: 0 AF XY: 0.00152 AC XY: 51 AN XY: 33518

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

African (AFR) AF: 0.00126 AC: 26 AN: 20638

American (AMR) AF: 0.00200 AC: 10 AN: 5012

Ashkenazi Jewish (ASJ) AF: 0.000867 AC: 2 AN: 2306

East Asian (EAS) AF: 0.00249 AC: 5 AN: 2008

South Asian (SAS) AF: 0.00130 AC: 2 AN: 1542

European-Finnish (FIN) AF: 0.00145 AC: 1 AN: 690

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

European-Non Finnish (NFE) AF: 0.00219 AC: 93 AN: 42474

Other (OTH) AF: 0.00 AC: 0 AN: 990

⚠️ 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;