Variant chr20-38304245-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001725.3(BPI):c.22G>A(p.Ala8Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0076 in 1,614,112 control chromosomes in the GnomAD database, including 69 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 0.0063 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0077 ( 64 hom. )

Consequence

BPI
NM_001725.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.692

Variant links:

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]

BPI links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002578646).

BP6

Variant 20-38304245-G-A is Benign according to our data. Variant chr20-38304245-G-A is described in ClinVar as [Benign]. Clinvar id is 785837.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
BPI	NM_001725.3 linkuse as main transcript	c.22G>A	p.Ala8Thr	missense_variant	1/15	ENST00000642449.2	NP_001716.3
BPI	XM_047440393.1 linkuse as main transcript	c.34G>A	p.Ala12Thr	missense_variant	1/13		XP_047296349.1
BPI	XM_047440394.1 linkuse as main transcript	c.34G>A	p.Ala12Thr	missense_variant	1/12		XP_047296350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
BPI	ENST00000642449.2 linkuse as main transcript	c.22G>A	p.Ala8Thr	missense_variant	1/15		NM_001725.3	ENSP00000494528	P1
BPI	ENST00000262865.9 linkuse as main transcript	c.34G>A	p.Ala12Thr	missense_variant	1/15	1		ENSP00000262865
	ENST00000437016.1 linkuse as main transcript	n.184-14499C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00631

AC:

960

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00394

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00602

Gnomad ASJ

AF:

0.0222

Gnomad EAS

AF:

0.00174

Gnomad SAS

AF:

0.00932

Gnomad FIN

AF:

0.000848

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00800

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00669

AC:

1680

AN:

250942

Hom.:

AF XY:

0.00738

AC XY:

1003

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.00439

Gnomad AMR exome

AF:

0.00393

Gnomad ASJ exome

AF:

0.0216

Gnomad EAS exome

AF:

0.000654

Gnomad SAS exome

AF:

0.00977

Gnomad FIN exome

AF:

0.00148

Gnomad NFE exome

AF:

0.00755

Gnomad OTH exome

AF:

0.00931

GnomAD4 exome

AF:

0.00774

AC:

11314

AN:

1461848

Hom.:

Cov.:

AF XY:

0.00788

AC XY:

5730

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00451

Gnomad4 AMR exome

AF:

0.00425

Gnomad4 ASJ exome

AF:

0.0216

Gnomad4 EAS exome

AF:

0.000680

Gnomad4 SAS exome

AF:

0.0102

Gnomad4 FIN exome

AF:

0.00129

Gnomad4 NFE exome

AF:

0.00795

Gnomad4 OTH exome

AF:

0.00884

GnomAD4 genome

AF:

0.00630

AC:

960

AN:

152264

Hom.:

Cov.:

AF XY:

0.00563

AC XY:

419

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00395

Gnomad4 AMR

AF:

0.00601

Gnomad4 ASJ

AF:

0.0222

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.00974

Gnomad4 FIN

AF:

0.000848

Gnomad4 NFE

AF:

0.00798

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00873

Hom.:

Bravo

AF:

0.00703

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.00431

AC:

ESP6500EA

AF:

0.0100

AC:

ExAC

AF:

0.00689

AC:

836

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.00976

EpiControl

AF:

0.0106

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.057

DANN

Benign

0.83

DEOGEN2

Benign

0.0037

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.33

MetaRNN

Benign

0.0026

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

0.0

REVEL

Benign

0.035

Sift

Benign

0.55

Sift4G

Benign

0.54

Polyphen

0.062

Vest4

0.076

MVP

0.040

MPC

0.049

ClinPred

0.0016

GERP RS

-5.0

Varity_R

0.019

gMVP

0.15

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over