20-38318446-G-C

Variant names:

• chr20-38318446-G-C
• rs4358188
• NM_001725.3:c.634G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001725.3(BPI):​c.634G>C​(p.Glu212Gln) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BPI NM_001725.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056386918).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BPI	NM_001725.3	c.634G>C	p.Glu212Gln	missense_variant	Exon 6 of 15	ENST00000642449.2	NP_001716.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BPI	ENST00000642449.2	c.634G>C	p.Glu212Gln	missense_variant	Exon 6 of 15		NM_001725.3	ENSP00000494528.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 53

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.14
DANN	Benign	0.78
DEOGEN2	Benign	0.0070	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.37	T;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.056	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.84	N;.
REVEL	Benign	0.014
Sift	Benign	0.21	T;.
Sift4G	Benign	0.093	T;T
Polyphen		0.013	B;.
Vest4		0.12
MutPred		0.45		Loss of disorder (P = 0.1531);.;
MVP		0.11
MPC		0.050
ClinPred		0.044	T
GERP RS		0.59
Varity_R		0.18
gMVP		0.25

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

LitVar

Other links and lift over

dbSNP: rs4358188; hg19: chr20-36946848;