chr20-38310510-G-A

Position:

• chr20-38310510-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001725.3(BPI):​c.394G>A​(p.Asp132Asn) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BPI NM_001725.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.355

Genes affected

BPI (HGNC:1095): (bactericidal permeability increasing protein) This gene encodes a lipopolysaccharide binding protein. It is associated with human neutrophil granules and has antimicrobial activity against gram-negative organisms. [provided by RefSeq, Nov 2014]

ENSG00000206249 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13236612).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPI	NM_001725.3	c.394G>A	p.Asp132Asn	missense_variant	4/15	ENST00000642449.2	NP_001716.3
BPI	XM_047440393.1	c.406G>A	p.Asp136Asn	missense_variant	4/13		XP_047296349.1
BPI	XM_047440394.1	c.406G>A	p.Asp136Asn	missense_variant	4/12		XP_047296350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BPI	ENST00000642449.2	c.394G>A	p.Asp132Asn	missense_variant	4/15		NM_001725.3	ENSP00000494528.2
BPI	ENST00000262865.9	c.406G>A	p.Asp136Asn	missense_variant	4/15	1		ENSP00000262865.5
ENSG00000206249	ENST00000437016.1	n.183+15844C>T		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 04, 2024

The c.406G>A (p.D136N) alteration is located in exon 4 (coding exon 4) of the BPI gene. This alteration results from a G to A substitution at nucleotide position 406, causing the aspartic acid (D) at amino acid position 136 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.073
Sift	Benign	0.17	T
Sift4G	Benign	0.34	T
Polyphen		0.041	B
Vest4		0.062
MutPred		0.67		Gain of MoRF binding (P = 0.0499);
MVP		0.19
MPC		0.059
ClinPred		0.41	T
GERP RS		0.36
Varity_R		0.16
gMVP		0.36

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-36938912;