22-32445713-GAAAAAAAAAAAA-GAAAAAAAAAAAAAAAAAA

Variant names:

• chr22-32445713-G-GAAAAAA
• rs61507713
• NM_174932.3:c.531-21_531-16dupTTTTTT

Variant summary

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

The NM_174932.3(BPIFC):​c.531-21_531-16dupTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00305 in 709,512 control chromosomes in the GnomAD database, including 50 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0016 (3 hom., cov: 0)
  • Exomes 𝑓: 0.0032 (47 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 119 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.531-21_531-16dupTTTTTT		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_531-15insTTTTTT		intron	N/A	ENSP00000300399.3	Q8NFQ6-1
	BPIFC	ENST00000397452.5	TSL:5	c.531-16_531-15insTTTTTT		intron	N/A	ENSP00000380594.1	Q8NFQ6-1
	BPIFC	ENST00000534972.4	TSL:5	n.*236-16_*236-15insTTTTTT		intron	N/A	ENSP00000439123.3	A0A8C8NLL8

Frequencies

GnomAD3 genomes AF: 0.00155 AC: 119 AN: 76570 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.000920

Gnomad AMI AF: 0.00341

Gnomad AMR AF: 0.00219

Gnomad ASJ AF: 0.000430

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.00257

Gnomad FIN AF: 0.00288

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00171

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00323 AC: 2043 AN: 632928 Hom.: 47 Cov.: 25 AF XY: 0.00342 AC XY: 1095 AN XY: 319910

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

African (AFR) AF: 0.00251 AC: 41 AN: 16352

American (AMR) AF: 0.00855 AC: 124 AN: 14508

Ashkenazi Jewish (ASJ) AF: 0.00379 AC: 44 AN: 11612

East Asian (EAS) AF: 0.00552 AC: 131 AN: 23732

South Asian (SAS) AF: 0.0110 AC: 429 AN: 38980

European-Finnish (FIN) AF: 0.00451 AC: 101 AN: 22384

Middle Eastern (MID) AF: 0.00358 AC: 7 AN: 1958

European-Non Finnish (NFE) AF: 0.00227 AC: 1078 AN: 475436

Other (OTH) AF: 0.00315 AC: 88 AN: 27966

⚠️ 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: 0.00155 AC: 119 AN: 76584 Hom.: 3 Cov.: 0 AF XY: 0.00152 AC XY: 51 AN XY: 33658

African (AFR) AF: 0.000919 AC: 19 AN: 20666

American (AMR) AF: 0.00219 AC: 11 AN: 5028

Ashkenazi Jewish (ASJ) AF: 0.000430 AC: 1 AN: 2326

East Asian (EAS) AF: 0.00348 AC: 7 AN: 2014

South Asian (SAS) AF: 0.00259 AC: 4 AN: 1544

European-Finnish (FIN) AF: 0.00288 AC: 2 AN: 694

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

European-Non Finnish (NFE) AF: 0.00171 AC: 73 AN: 42652

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

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;