NM_001725.3:c.634G>C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E212K) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BPI NM_001725.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 59 publications found

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

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=0.056386918).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001725.3. 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
	BPI	NM_001725.3	MANE Select	c.634G>C	p.Glu212Gln	missense	Exon 6 of 15	NP_001716.3	A0A2R8YDF1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPI	ENST00000642449.2	MANE Select	c.634G>C	p.Glu212Gln	missense	Exon 6 of 15	ENSP00000494528.2	A0A2R8YDF1
	BPI	ENST00000262865.10	TSL:1	c.634G>C	p.Glu212Gln	missense	Exon 9 of 16	ENSP00000262865.5	P17213
	BPI	ENST00000716802.1		c.634G>C	p.Glu212Gln	missense	Exon 8 of 17	ENSP00000520600.1	A0A2R8YDF1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 53

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 49407

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.1
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.014
Sift	Benign	0.21	T
Sift4G	Benign	0.093	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
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs4358188; hg19: chr20-36946848;