22-32445713-GAAAAAAAAAAAA-GAAAAAAAAAAAAAAAAA

Variant names:

• chr22-32445713-G-GAAAAA
• rs61507713
• NM_174932.3:c.531-20_531-16dupTTTTT

Variant summary

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

The NM_174932.3(BPIFC):​c.531-20_531-16dupTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00967 in 706,894 control chromosomes in the GnomAD database, including 166 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0090 (23 hom., cov: 0)
  • Exomes 𝑓: 0.0097 (143 hom.)
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 692 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.531-20_531-16dupTTTTT		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_531-15insTTTTT		intron	N/A	ENSP00000300399.3	Q8NFQ6-1
	BPIFC	ENST00000397452.5	TSL:5	c.531-16_531-15insTTTTT		intron	N/A	ENSP00000380594.1	Q8NFQ6-1
	BPIFC	ENST00000534972.4	TSL:5	n.*236-16_*236-15insTTTTT		intron	N/A	ENSP00000439123.3	A0A8C8NLL8

Frequencies

GnomAD3 genomes AF: 0.00904 AC: 692 AN: 76518 Hom.: 23 Cov.: 0

Gnomad AFR AF: 0.00523

Gnomad AMI AF: 0.0103

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.0125

Gnomad EAS AF: 0.0134

Gnomad SAS AF: 0.0129

Gnomad FIN AF: 0.00432

Gnomad MID AF: 0.0132

Gnomad NFE AF: 0.0101

Gnomad OTH AF: 0.00703

GnomAD4 exome AF: 0.00974 AC: 6142 AN: 630362 Hom.: 143 Cov.: 25 AF XY: 0.0105 AC XY: 3350 AN XY: 318608

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

African (AFR) AF: 0.00730 AC: 119 AN: 16292

American (AMR) AF: 0.0178 AC: 257 AN: 14418

Ashkenazi Jewish (ASJ) AF: 0.0109 AC: 126 AN: 11540

East Asian (EAS) AF: 0.0122 AC: 289 AN: 23594

South Asian (SAS) AF: 0.0284 AC: 1100 AN: 38768

European-Finnish (FIN) AF: 0.0126 AC: 281 AN: 22224

Middle Eastern (MID) AF: 0.0113 AC: 22 AN: 1952

European-Non Finnish (NFE) AF: 0.00780 AC: 3696 AN: 473770

Other (OTH) AF: 0.00906 AC: 252 AN: 27804

⚠️ 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 AF: 0.00904 AC: 692 AN: 76532 Hom.: 23 Cov.: 0 AF XY: 0.00913 AC XY: 307 AN XY: 33632

African (AFR) AF: 0.00523 AC: 108 AN: 20660

American (AMR) AF: 0.0117 AC: 59 AN: 5024

Ashkenazi Jewish (ASJ) AF: 0.0125 AC: 29 AN: 2320

East Asian (EAS) AF: 0.0134 AC: 27 AN: 2012

South Asian (SAS) AF: 0.0130 AC: 20 AN: 1540

European-Finnish (FIN) AF: 0.00432 AC: 3 AN: 694

Middle Eastern (MID) AF: 0.0132 AC: 1 AN: 76

European-Non Finnish (NFE) AF: 0.0101 AC: 432 AN: 42628

Other (OTH) AF: 0.00701 AC: 7 AN: 998

Alfa AF: 0.0193 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

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;