22-32445713-GAAAAAAAAAAAA-GAAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr22-32445713-G-GAAAAAAAAAA
• rs61507713
• NM_174932.3:c.531-25_531-16dupTTTTTTTTTT

Variant summary

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

The NM_174932.3(BPIFC):​c.531-25_531-16dupTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00364 in 709,890 control chromosomes in the GnomAD database, including 17 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0045 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0035 (16 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 341 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.531-25_531-16dupTTTTTTTTTT		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_531-15insTTTTTTTTTT		intron	N/A	ENSP00000300399.3	Q8NFQ6-1
	BPIFC	ENST00000397452.5	TSL:5	c.531-16_531-15insTTTTTTTTTT		intron	N/A	ENSP00000380594.1	Q8NFQ6-1
	BPIFC	ENST00000534972.4	TSL:5	n.*236-16_*236-15insTTTTTTTTTT		intron	N/A	ENSP00000439123.3	A0A8C8NLL8

Frequencies

GnomAD3 genomes AF: 0.00447 AC: 341 AN: 76302 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00320

Gnomad AMI AF: 0.0137

Gnomad AMR AF: 0.00339

Gnomad ASJ AF: 0.00216

Gnomad EAS AF: 0.00694

Gnomad SAS AF: 0.00322

Gnomad FIN AF: 0.00144

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00523

Gnomad OTH AF: 0.00302

GnomAD4 exome AF: 0.00354 AC: 2246 AN: 633574 Hom.: 16 Cov.: 25 AF XY: 0.00404 AC XY: 1294 AN XY: 320220

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

African (AFR) AF: 0.00183 AC: 30 AN: 16396

American (AMR) AF: 0.00625 AC: 91 AN: 14562

Ashkenazi Jewish (ASJ) AF: 0.00448 AC: 52 AN: 11620

East Asian (EAS) AF: 0.00547 AC: 130 AN: 23760

South Asian (SAS) AF: 0.00875 AC: 342 AN: 39102

European-Finnish (FIN) AF: 0.00505 AC: 113 AN: 22382

Middle Eastern (MID) AF: 0.000510 AC: 1 AN: 1960

European-Non Finnish (NFE) AF: 0.00289 AC: 1373 AN: 475786

Other (OTH) AF: 0.00407 AC: 114 AN: 28006

⚠️ 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: 0.00447 AC: 341 AN: 76316 Hom.: 1 Cov.: 0 AF XY: 0.00459 AC XY: 154 AN XY: 33550

African (AFR) AF: 0.00320 AC: 66 AN: 20622

American (AMR) AF: 0.00339 AC: 17 AN: 5014

Ashkenazi Jewish (ASJ) AF: 0.00216 AC: 5 AN: 2320

East Asian (EAS) AF: 0.00695 AC: 14 AN: 2014

South Asian (SAS) AF: 0.00324 AC: 5 AN: 1542

European-Finnish (FIN) AF: 0.00144 AC: 1 AN: 694

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

European-Non Finnish (NFE) AF: 0.00523 AC: 222 AN: 42458

Other (OTH) AF: 0.00302 AC: 3 AN: 994

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;