20-33081586-C-G

Variant names:

• chr20-33081586-C-G
• NM_182519.3:c.60C>G
• BPIFB4 p.His20Gln

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_182519.3(BPIFB4):​c.60C>G​(p.His20Gln) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BPIFB4 NM_182519.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45
• Publications: 0 publications found

Genes affected

BPIFB4 (HGNC:16179): (BPI fold containing family B member 4) Predicted to enable lipid binding activity. Predicted to be located in cytoplasm and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04508391).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182519.3. 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
	BPIFB4	NM_182519.3	MANE Select	c.60C>G	p.His20Gln	missense	Exon 3 of 18	NP_872325.2	P59827-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPIFB4	ENST00000375483.4	TSL:5 MANE Select	c.60C>G	p.His20Gln	missense	Exon 3 of 18	ENSP00000364632.3	P59827-1
	BPIFB4	ENST00000674031.1		c.60C>G	p.His20Gln	missense	Exon 1 of 15	ENSP00000501266.1	A0A669KBJ0
	BPIFB4	ENST00000445356.1	TSL:2	n.60C>G		non_coding_transcript_exon	Exon 3 of 7	ENSP00000388423.1	F8WEG9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.41
DANN	Benign	0.42
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.97	N
PhyloP100		1.5
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.46	N
REVEL	Benign	0.013
Sift	Benign	1.0	T
Sift4G	Benign	0.54	T
PromoterAI		-0.031	Neutral
Varity_R		0.037
gMVP		0.033
Mutation Taster		=99/1	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr20-31669392;