20-38311912-C-T

Position:

• chr20-38311912-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.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. 14/20 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

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=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 id 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/exons	MANE	UniProt
BPI	NM_001725.3	c.575C>T	p.Ala192Val	missense_variant	5/15	ENST00000642449.2
BPI	XM_047440393.1	c.587C>T	p.Ala196Val	missense_variant	5/13
BPI	XM_047440394.1	c.587C>T	p.Ala196Val	missense_variant	5/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BPI	ENST00000642449.2	c.575C>T	p.Ala192Val	missense_variant	5/15		NM_001725.3	P1
BPI	ENST00000262865.9	c.587C>T	p.Ala196Val	missense_variant	5/15	1
	ENST00000437016.1	n.183+14442G>A		intron_variant, non_coding_transcript_variant		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

GnomAD3 exomes AF: 0.0545 AC: 13707 AN: 251404 Hom.: 496 AF XY: 0.0601 AC XY: 8170 AN XY: 135884

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 SAS exome AF: 0.118

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

Gnomad4 AFR exome AF: 0.0188

Gnomad4 AMR exome AF: 0.0259

Gnomad4 ASJ exome AF: 0.0608

Gnomad4 EAS exome AF: 0.0360

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.0270

Gnomad4 NFE exome AF: 0.0570

Gnomad4 OTH exome AF: 0.0575

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

Gnomad4 AFR AF: 0.0211

Gnomad4 AMR AF: 0.0367

Gnomad4 ASJ AF: 0.0582

Gnomad4 EAS AF: 0.0516

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.0234

Gnomad4 NFE AF: 0.0572

Gnomad4 OTH AF: 0.0496

Alfa AF: 0.0551 Hom.: 660

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

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: MAF -

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	0.11
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
MutationTaster	Benign	1.0	N
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs5743509; hg19: chr20-36940314; COSMIC: COSV53406605;