rs2076054

Variant names:

• chr22-32436887-C-T
• rs2076054
• NM_174932.3:c.747+873G>A

Variant summary

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

The NM_174932.3(BPIFC):​c.747+873G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 152,118 control chromosomes in the GnomAD database, including 34,769 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 0.66 (34769 hom., cov: 33)
• Consequence: BPIFC NM_174932.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.892
• Publications: 8 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BPIFC	NM_174932.3	c.747+873G>A		intron_variant	Intron 9 of 16	ENST00000300399.9	NP_777592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BPIFC	ENST00000300399.9	c.747+873G>A		intron_variant	Intron 9 of 16	1	NM_174932.3	ENSP00000300399.3
BPIFC	ENST00000397452.5	c.747+873G>A		intron_variant	Intron 8 of 15	5		ENSP00000380594.1
BPIFC	ENST00000534972.4	n.*452+873G>A		intron_variant	Intron 8 of 14	5		ENSP00000439123.3

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100488 AN: 152000 Hom.: 34746 Cov.: 33

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.726

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.774

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.690

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

GnomAD4 genome AF: 0.661 AC: 100548 AN: 152118 Hom.: 34769 Cov.: 33 AF XY: 0.665 AC XY: 49399 AN XY: 74336

African (AFR) AF: 0.431 AC: 17872 AN: 41480

American (AMR) AF: 0.726 AC: 11098 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.751 AC: 2608 AN: 3472

East Asian (EAS) AF: 0.722 AC: 3739 AN: 5182

South Asian (SAS) AF: 0.838 AC: 4042 AN: 4822

European-Finnish (FIN) AF: 0.704 AC: 7432 AN: 10558

Middle Eastern (MID) AF: 0.757 AC: 221 AN: 292

European-Non Finnish (NFE) AF: 0.755 AC: 51329 AN: 68000

Other (OTH) AF: 0.693 AC: 1465 AN: 2114

Alfa AF: 0.729 Hom.: 179340

Bravo AF: 0.649

Asia WGS AF: 0.759 AC: 2633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.27
DANN	Benign	0.58
PhyloP100		-0.89
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: rs2076054; hg19: chr22-32832874;