22-32445713-GAAAAAAAAAAAA-GAAAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr22-32445713-G-GAAAAAAAAAAA
• rs61507713
• NM_174932.3:c.531-26_531-16dupTTTTTTTTTTT

Variant summary

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

The NM_174932.3(BPIFC):​c.531-26_531-16dupTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00534 in 631,654 control chromosomes in the GnomAD database, including 22 homozygotes. 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. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0062 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0053 (22 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.531-26_531-16dupTTTTTTTTTTT		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_531-15insTTTTTTTTTTT		intron	N/A	ENSP00000300399.3	Q8NFQ6-1
	BPIFC	ENST00000397452.5	TSL:5	c.531-16_531-15insTTTTTTTTTTT		intron	N/A	ENSP00000380594.1	Q8NFQ6-1
	BPIFC	ENST00000534972.4	TSL:5	n.*236-16_*236-15insTTTTTTTTTTT		intron	N/A	ENSP00000439123.3	A0A8C8NLL8

Frequencies

GnomAD3 genomes AF: 0.00615 AC: 467 AN: 75906 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00488

Gnomad AMI AF: 0.0190

Gnomad AMR AF: 0.00440

Gnomad ASJ AF: 0.00910

Gnomad EAS AF: 0.00199

Gnomad SAS AF: 0.00193

Gnomad FIN AF: 0.00434

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00709

Gnomad OTH AF: 0.00403

GnomAD4 exome AF: 0.00534 AC: 3376 AN: 631654 Hom.: 22 Cov.: 25 AF XY: 0.00606 AC XY: 1935 AN XY: 319062

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

African (AFR) AF: 0.00386 AC: 63 AN: 16330

American (AMR) AF: 0.00794 AC: 115 AN: 14476

Ashkenazi Jewish (ASJ) AF: 0.00546 AC: 63 AN: 11546

East Asian (EAS) AF: 0.00586 AC: 139 AN: 23726

South Asian (SAS) AF: 0.0167 AC: 649 AN: 38840

European-Finnish (FIN) AF: 0.00606 AC: 135 AN: 22292

Middle Eastern (MID) AF: 0.00511 AC: 10 AN: 1958

European-Non Finnish (NFE) AF: 0.00434 AC: 2059 AN: 474608

Other (OTH) AF: 0.00513 AC: 143 AN: 27878

⚠️ 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: 0.00615 AC: 467 AN: 75920 Hom.: 1 Cov.: 0 AF XY: 0.00681 AC XY: 227 AN XY: 33350

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

African (AFR) AF: 0.00487 AC: 100 AN: 20528

American (AMR) AF: 0.00440 AC: 22 AN: 5004

Ashkenazi Jewish (ASJ) AF: 0.00910 AC: 21 AN: 2308

East Asian (EAS) AF: 0.00200 AC: 4 AN: 2002

South Asian (SAS) AF: 0.00195 AC: 3 AN: 1542

European-Finnish (FIN) AF: 0.00434 AC: 3 AN: 692

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

European-Non Finnish (NFE) AF: 0.00709 AC: 299 AN: 42196

Other (OTH) AF: 0.00402 AC: 4 AN: 994

⚠️ 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;