20-38311912-C-T

Variant names:

• chr20-38311912-C-T
• rs5743509
• NM_001725.3:c.575C>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.575C>T​(p.Ala192Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0559 in 1,613,722 control chromosomes in the GnomAD database, including 2,878 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.044 (179 hom., cov: 31)
  • Exomes 𝑓: 0.057 (2699 hom.)
• Consequence: BPI NM_001725.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.251
• Publications: 27 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=0.0019894242).
• BP6: Variant 20-38311912-C-T is Benign according to our data. Variant chr20-38311912-C-T is described in ClinVar as Benign. ClinVar VariationId is 402433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BPI	NM_001725.3	c.575C>T	p.Ala192Val	missense_variant	Exon 5 of 15	ENST00000642449.2	NP_001716.3
BPI	XM_047440393.1	c.587C>T	p.Ala196Val	missense_variant	Exon 5 of 13		XP_047296349.1
BPI	XM_047440394.1	c.587C>T	p.Ala196Val	missense_variant	Exon 5 of 12		XP_047296350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BPI	ENST00000642449.2	c.575C>T	p.Ala192Val	missense_variant	Exon 5 of 15		NM_001725.3	ENSP00000494528.2

Frequencies

GnomAD3 genomes AF: 0.0438 AC: 6657 AN: 152022 Hom.: 173 Cov.: 31

Gnomad AFR AF: 0.0206

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0368

Gnomad ASJ AF: 0.0582

Gnomad EAS AF: 0.0517

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0234

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0572

Gnomad OTH AF: 0.0463

GnomAD2 exomes AF: 0.0545 AC: 13707 AN: 251404 AF XY: 0.0601

Gnomad AFR exome AF: 0.0196

Gnomad AMR exome AF: 0.0241

Gnomad ASJ exome AF: 0.0616

Gnomad EAS exome AF: 0.0485

Gnomad FIN exome AF: 0.0252

Gnomad NFE exome AF: 0.0576

Gnomad OTH exome AF: 0.0549

GnomAD4 exome AF: 0.0571 AC: 83482 AN: 1461582 Hom.: 2699 Cov.: 31 AF XY: 0.0594 AC XY: 43191 AN XY: 727084

African (AFR) AF: 0.0188 AC: 630 AN: 33478

American (AMR) AF: 0.0259 AC: 1158 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 1589 AN: 26134

East Asian (EAS) AF: 0.0360 AC: 1428 AN: 39694

South Asian (SAS) AF: 0.115 AC: 9886 AN: 86232

European-Finnish (FIN) AF: 0.0270 AC: 1444 AN: 53416

Middle Eastern (MID) AF: 0.0881 AC: 503 AN: 5712

European-Non Finnish (NFE) AF: 0.0570 AC: 63371 AN: 1111810

Other (OTH) AF: 0.0575 AC: 3473 AN: 60382

GnomAD4 genome AF: 0.0439 AC: 6682 AN: 152140 Hom.: 179 Cov.: 31 AF XY: 0.0430 AC XY: 3197 AN XY: 74378

African (AFR) AF: 0.0211 AC: 876 AN: 41512

American (AMR) AF: 0.0367 AC: 561 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0582 AC: 202 AN: 3470

East Asian (EAS) AF: 0.0516 AC: 267 AN: 5174

South Asian (SAS) AF: 0.106 AC: 509 AN: 4794

European-Finnish (FIN) AF: 0.0234 AC: 248 AN: 10606

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0572 AC: 3889 AN: 67988

Other (OTH) AF: 0.0496 AC: 105 AN: 2116

Alfa AF: 0.0534 Hom.: 873

Bravo AF: 0.0423

TwinsUK AF: 0.0539 AC: 200

ALSPAC AF: 0.0620 AC: 239

ESP6500AA AF: 0.0197 AC: 87

ESP6500EA AF: 0.0551 AC: 474

ExAC AF: 0.0573 AC: 6951

Asia WGS AF: 0.0920 AC: 320 AN: 3478

EpiCase AF: 0.0624

EpiControl AF: 0.0590

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: MAF -

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	0.11
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.4
DANN	Benign	0.93
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.25
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.022
Sift	Benign	0.18	T
Sift4G	Benign	0.21	T
Polyphen		0.79	P
Vest4		0.029
MPC		0.051
ClinPred		0.0053	T
GERP RS		0.46
Varity_R		0.12
gMVP		0.16
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs5743509; hg19: chr20-36940314; COSMIC: COSV53406605;