chr20-38304258-C-G

Position:

• chr20-38304258-C-G

Variant summary

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

The NM_001725.3(BPI):​c.35C>G​(p.Ala12Gly) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A12T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BPI NM_001725.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70

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=0.21886048).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPI	NM_001725.3	c.35C>G	p.Ala12Gly	missense_variant	1/15	ENST00000642449.2	NP_001716.3
BPI	XM_047440393.1	c.47C>G	p.Ala16Gly	missense_variant	1/13		XP_047296349.1
BPI	XM_047440394.1	c.47C>G	p.Ala16Gly	missense_variant	1/12		XP_047296350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BPI	ENST00000642449.2	c.35C>G	p.Ala12Gly	missense_variant	1/15		NM_001725.3	ENSP00000494528.2
BPI	ENST00000262865.9	c.47C>G	p.Ala16Gly	missense_variant	1/15	1		ENSP00000262865.5
ENSG00000285144	ENST00000418004.5	n.433C>G		non_coding_transcript_exon_variant	3/3	4		ENSP00000520599.1
ENSG00000206249	ENST00000437016.1	n.184-14512G>C		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 64

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.5	L
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.066
Sift	Benign	0.079	T
Sift4G	Benign	0.13	T
Polyphen		0.95	P
Vest4		0.35
MutPred		0.35		Loss of loop (P = 0.0374);
MVP		0.25
MPC		0.29
ClinPred		0.98	D
GERP RS		2.8
Varity_R		0.053
gMVP		0.21

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

LitVar

Other links and lift over

dbSNP: rs1341023; hg19: chr20-36932660;