chr22-32453725-C-A

Variant names:

• chr22-32453725-C-A
• rs11703151
• NM_174932.3:c.125-222G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_174932.3(BPIFC):​c.125-222G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,158 control chromosomes in the GnomAD database, including 1,791 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1791 hom., cov: 32)
• Consequence: BPIFC NM_174932.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

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.125-222G>T		intron	N/A	NP_777592.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPIFC	ENST00000300399.9	TSL:1 MANE Select	c.125-222G>T		intron	N/A	ENSP00000300399.3
	BPIFC	ENST00000397450.2	TSL:1	c.125-222G>T		intron	N/A	ENSP00000380592.1
	BPIFC	ENST00000397452.5	TSL:5	c.125-222G>T		intron	N/A	ENSP00000380594.1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20857 AN: 152040 Hom.: 1794 Cov.: 32

Gnomad AFR AF: 0.0589

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.0294

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.146

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.137 AC: 20856 AN: 152158 Hom.: 1791 Cov.: 32 AF XY: 0.133 AC XY: 9902 AN XY: 74378

African (AFR) AF: 0.0588 AC: 2443 AN: 41518

American (AMR) AF: 0.126 AC: 1926 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 661 AN: 3468

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5174

South Asian (SAS) AF: 0.0290 AC: 140 AN: 4826

European-Finnish (FIN) AF: 0.174 AC: 1837 AN: 10584

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13255 AN: 68004

Other (OTH) AF: 0.144 AC: 304 AN: 2108

Alfa AF: 0.168 Hom.: 7715

Bravo AF: 0.132

Asia WGS AF: 0.0270 AC: 92 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.73
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11703151; hg19: chr22-32849712;