rs140684884

Variant names:

• chr22-32432447-C-G
• rs140684884
• NM_174932.3:c.1075G>C

Your query was ambiguous. Multiple possible variants found:

• chr22-32432447-C-G
• chr22-32432447-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_174932.3(BPIFC):​c.1075G>C​(p.Asp359His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D359N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BPIFC NM_174932.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35430208).

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.1075G>C	p.Asp359His	missense	Exon 12 of 17	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.1075G>C	p.Asp359His	missense	Exon 12 of 17	ENSP00000300399.3	Q8NFQ6-1
	BPIFC	ENST00000397452.5	TSL:5	c.1075G>C	p.Asp359His	missense	Exon 11 of 16	ENSP00000380594.1	Q8NFQ6-1
	BPIFC	ENST00000534972.4	TSL:5	n.*684-1033G>C		intron	N/A	ENSP00000439123.3	A0A8C8NLL8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0029	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		2.0
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.19
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.010	D
Polyphen		0.97	D
Vest4		0.38
MutPred		0.49		Loss of catalytic residue at D359 (P = 0.1026)
MVP		0.48
MPC		0.42
ClinPred		0.96	D
GERP RS		4.9
Varity_R		0.29
gMVP		0.53
Mutation Taster		=87/13	polymorphism

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: rs140684884; hg19: chr22-32828434;