20-38304258-C-T

Variant names:

• chr20-38304258-C-T
• rs1341023
• NM_001725.3:c.35C>T

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as 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
• Publications: 39 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: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
BPI	NM_001725.3	c.35C>T	p.Ala12Val	missense_variant	Exon 1 of 15	ENST00000642449.2	NP_001716.3
BPI	XM_047440393.1	c.47C>T	p.Ala16Val	missense_variant	Exon 1 of 13		XP_047296349.1
BPI	XM_047440394.1	c.47C>T	p.Ala16Val	missense_variant	Exon 1 of 12		XP_047296350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BPI	ENST00000642449.2	c.35C>T	p.Ala12Val	missense_variant	Exon 1 of 15		NM_001725.3	ENSP00000494528.2

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

GnomAD2 exomes AF: 0.512 AC: 128441 AN: 250810 AF XY: 0.516

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 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

African (AFR) AF: 0.199 AC: 6672 AN: 33476

American (AMR) AF: 0.555 AC: 24793 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 17046 AN: 26134

East Asian (EAS) AF: 0.607 AC: 24087 AN: 39690

South Asian (SAS) AF: 0.498 AC: 42961 AN: 86236

European-Finnish (FIN) AF: 0.445 AC: 23750 AN: 53396

Middle Eastern (MID) AF: 0.566 AC: 3264 AN: 5766

European-Non Finnish (NFE) AF: 0.542 AC: 602664 AN: 1111812

Other (OTH) AF: 0.521 AC: 31449 AN: 60386

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

African (AFR) AF: 0.211 AC: 8764 AN: 41462

American (AMR) AF: 0.506 AC: 7736 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2182 AN: 3466

East Asian (EAS) AF: 0.564 AC: 2910 AN: 5156

South Asian (SAS) AF: 0.479 AC: 2307 AN: 4820

European-Finnish (FIN) AF: 0.431 AC: 4559 AN: 10570

Middle Eastern (MID) AF: 0.565 AC: 165 AN: 292

European-Non Finnish (NFE) AF: 0.532 AC: 36184 AN: 67952

Other (OTH) AF: 0.503 AC: 1062 AN: 2112

Alfa AF: 0.508 Hom.: 35521

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

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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
PhyloP100		1.7
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
PromoterAI		0.022	Neutral
Varity_R		0.036
gMVP		0.27
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1341023; hg19: chr20-36932660; COSMIC: COSV53404234;