chr22-32445713-G-GAAAAAAAAA

Variant names:

• chr22-32445713-G-GAAAAAAAAA
• rs61507713
• NM_174932.3:c.531-24_531-16dupTTTTTTTTT

Variant summary

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

The NM_174932.3(BPIFC):​c.531-24_531-16dupTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 710,758 control chromosomes in the GnomAD database, including 18 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0018 (18 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 154 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.531-24_531-16dupTTTTTTTTT		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_531-15insTTTTTTTTT		intron	N/A	ENSP00000300399.3	Q8NFQ6-1
	BPIFC	ENST00000397452.5	TSL:5	c.531-16_531-15insTTTTTTTTT		intron	N/A	ENSP00000380594.1	Q8NFQ6-1
	BPIFC	ENST00000534972.4	TSL:5	n.*236-16_*236-15insTTTTTTTTT		intron	N/A	ENSP00000439123.3	A0A8C8NLL8

Frequencies

GnomAD3 genomes AF: 0.00201 AC: 154 AN: 76518 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00155

Gnomad AMI AF: 0.00172

Gnomad AMR AF: 0.00259

Gnomad ASJ AF: 0.00172

Gnomad EAS AF: 0.00446

Gnomad SAS AF: 0.00129

Gnomad FIN AF: 0.00145

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00211

Gnomad OTH AF: 0.00201

GnomAD4 exome AF: 0.00179 AC: 1134 AN: 634226 Hom.: 18 Cov.: 25 AF XY: 0.00190 AC XY: 608 AN XY: 320566

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

African (AFR) AF: 0.00220 AC: 36 AN: 16400

American (AMR) AF: 0.00500 AC: 73 AN: 14596

Ashkenazi Jewish (ASJ) AF: 0.00206 AC: 24 AN: 11642

East Asian (EAS) AF: 0.00235 AC: 56 AN: 23792

South Asian (SAS) AF: 0.00444 AC: 174 AN: 39156

European-Finnish (FIN) AF: 0.00281 AC: 63 AN: 22408

Middle Eastern (MID) AF: 0.00203 AC: 4 AN: 1966

European-Non Finnish (NFE) AF: 0.00138 AC: 659 AN: 476238

Other (OTH) AF: 0.00161 AC: 45 AN: 28028

⚠️ 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: 0.00201 AC: 154 AN: 76532 Hom.: 0 Cov.: 0 AF XY: 0.00184 AC XY: 62 AN XY: 33640

African (AFR) AF: 0.00155 AC: 32 AN: 20664

American (AMR) AF: 0.00259 AC: 13 AN: 5022

Ashkenazi Jewish (ASJ) AF: 0.00172 AC: 4 AN: 2326

East Asian (EAS) AF: 0.00447 AC: 9 AN: 2012

South Asian (SAS) AF: 0.00130 AC: 2 AN: 1544

European-Finnish (FIN) AF: 0.00145 AC: 1 AN: 692

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

European-Non Finnish (NFE) AF: 0.00211 AC: 90 AN: 42616

Other (OTH) AF: 0.00200 AC: 2 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;