chr20-33301306-C-T

Variant names:

• chr20-33301306-C-T
• NM_033197.3:c.821C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033197.3(BPIFB1):​c.821C>T​(p.Thr274Ile) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BPIFB1 NM_033197.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.291
• Publications: 0 publications found

Genes affected

BPIFB1 (HGNC:16108): (BPI fold containing family B member 1) The protein encoded by this gene may be involved in the innate immune response to bacterial exposure in the mouth, nasal cavities, and lungs. The encoded protein is secreted and is a member of the BPI/LBP/PLUNC protein superfamily. This gene is found with other members of the superfamily in a cluster on chromosome 20. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07183346).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033197.3. 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
	BPIFB1	NM_033197.3	MANE Select	c.821C>T	p.Thr274Ile	missense	Exon 9 of 16	NP_149974.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPIFB1	ENST00000253354.2	TSL:1 MANE Select	c.821C>T	p.Thr274Ile	missense	Exon 9 of 16	ENSP00000253354.1	Q8TDL5-1
	BPIFB1	ENST00000865835.1		c.962C>T	p.Thr321Ile	missense	Exon 10 of 17	ENSP00000535894.1
	BPIFB1	ENST00000960544.1		c.962C>T	p.Thr321Ile	missense	Exon 10 of 17	ENSP00000630603.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.3
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.29
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.030
Sift	Benign	0.16	T
Sift4G	Benign	0.061	T
Polyphen		0.44	B
Vest4		0.088
MutPred		0.52		Loss of disorder (P = 0.2335)
MVP		0.092
MPC		0.18
ClinPred		0.30	T
GERP RS		-1.0
Varity_R		0.035
gMVP		0.13
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr20-31889112;