chr20-38304284-G-A

Position:

• chr20-38304284-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.61G>A​(p.Gly21Ser) 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. 15/21 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: BPI NM_001725.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.17

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]

(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=0.105657846).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPI	NM_001725.3	c.61G>A	p.Gly21Ser	missense_variant	1/15	ENST00000642449.2	NP_001716.3
BPI	XM_047440393.1	c.73G>A	p.Gly25Ser	missense_variant	1/13		XP_047296349.1
BPI	XM_047440394.1	c.73G>A	p.Gly25Ser	missense_variant	1/12		XP_047296350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BPI	ENST00000642449.2	c.61G>A	p.Gly21Ser	missense_variant	1/15		NM_001725.3	ENSP00000494528	P1
BPI	ENST00000262865.9	c.73G>A	p.Gly25Ser	missense_variant	1/15	1		ENSP00000262865
	ENST00000437016.1	n.184-14538C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

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

May 18, 2023

The c.73G>A (p.G25S) alteration is located in exon 1 (coding exon 1) of the BPI gene. This alteration results from a G to A substitution at nucleotide position 73, causing the glycine (G) at amino acid position 25 to be replaced by a serine (S). 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	0.13
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	13
DANN	Benign	0.87
DEOGEN2	Benign	0.0060	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.35	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.037
Sift	Benign	0.42	T
Sift4G	Benign	0.58	T
Polyphen		0.12	B
Vest4		0.14
MutPred		0.42		Gain of glycosylation at G25 (P = 0.007);
MVP		0.45
MPC		0.054
ClinPred		0.17	T
GERP RS		1.8
Varity_R		0.031
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr20-36932686;