20-38304258-C-T

Position:

• chr20-38304258-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001725.3(BPI):​c.35C>T​(p.Ala12Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 1,613,624 control chromosomes in the GnomAD database, including 225,681 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. 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: 𝑓 0.44 (16185 hom., cov: 32)
  • Exomes 𝑓: 0.53 (209496 hom.)
• Consequence: BPI NM_001725.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.4416378E-5).
• BP6: Variant 20-38304258-C-T is Benign according to our data. Variant chr20-38304258-C-T is described in ClinVar as [Benign]. Clinvar id is 402430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPI	NM_001725.3	c.35C>T	p.Ala12Val	missense_variant	1/15	ENST00000642449.2	NP_001716.3
BPI	XM_047440393.1	c.47C>T	p.Ala16Val	missense_variant	1/13		XP_047296349.1
BPI	XM_047440394.1	c.47C>T	p.Ala16Val	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>T	p.Ala12Val	missense_variant	1/15		NM_001725.3	ENSP00000494528	P1
BPI	ENST00000262865.9	c.47C>T	p.Ala16Val	missense_variant	1/15	1		ENSP00000262865
	ENST00000437016.1	n.184-14512G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66349 AN: 151904 Hom.: 16174 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.498

GnomAD3 exomes AF: 0.512 AC: 128441 AN: 250810 Hom.: 33929 AF XY: 0.516 AC XY: 70018 AN XY: 135748

Gnomad AFR exome AF: 0.198

Gnomad AMR exome AF: 0.560

Gnomad ASJ exome AF: 0.644

Gnomad EAS exome AF: 0.550

Gnomad SAS exome AF: 0.497

Gnomad FIN exome AF: 0.442

Gnomad NFE exome AF: 0.540

Gnomad OTH exome AF: 0.548

GnomAD4 exome AF: 0.531 AC: 776686 AN: 1461602 Hom.: 209496 Cov.: 64 AF XY: 0.531 AC XY: 385840 AN XY: 727090

Gnomad4 AFR exome AF: 0.199

Gnomad4 AMR exome AF: 0.555

Gnomad4 ASJ exome AF: 0.652

Gnomad4 EAS exome AF: 0.607

Gnomad4 SAS exome AF: 0.498

Gnomad4 FIN exome AF: 0.445

Gnomad4 NFE exome AF: 0.542

Gnomad4 OTH exome AF: 0.521

GnomAD4 genome AF: 0.437 AC: 66397 AN: 152022 Hom.: 16185 Cov.: 32 AF XY: 0.436 AC XY: 32397 AN XY: 74318

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.630

Gnomad4 EAS AF: 0.564

Gnomad4 SAS AF: 0.479

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.503

Alfa AF: 0.515 Hom.: 26826

Bravo AF: 0.439

TwinsUK AF: 0.544 AC: 2018

ALSPAC AF: 0.547 AC: 2108

ESP6500AA AF: 0.217 AC: 954

ESP6500EA AF: 0.535 AC: 4605

ExAC AF: 0.504 AC: 61236

Asia WGS AF: 0.539 AC: 1875 AN: 3478

EpiCase AF: 0.561

EpiControl AF: 0.562

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.49	T
MetaRNN	Benign	0.000024	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.050
Sift	Benign	0.15	T
Sift4G	Benign	0.11	T
Polyphen		0.80	P
Vest4		0.077
MPC		0.095
ClinPred		0.031	T
GERP RS		2.8
Varity_R		0.036
gMVP		0.27

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; COSMIC: COSV53404234;