Variant 20-38310650-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001725.3(BPI):c.534G>C(p.Val178=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,611,708 control chromosomes in the GnomAD database, including 9,717 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.086 ( 756 hom., cov: 32)

Exomes 𝑓: 0.11 ( 8961 hom. )

Consequence

BPI
NM_001725.3 splice_region, synonymous

Scores

Splicing: ADA: 0.0004263

Clinical Significance

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

Conservation

PhyloP100: 0.412

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 20-38310650-G-C is Benign according to our data. Variant chr20-38310650-G-C is described in ClinVar as [Benign]. Clinvar id is 402432.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.412 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
BPI	NM_001725.3 linkuse as main transcript	c.534G>C	p.Val178=	splice_region_variant, synonymous_variant	4/15	ENST00000642449.2	NP_001716.3
BPI	XM_047440393.1 linkuse as main transcript	c.546G>C	p.Val182=	splice_region_variant, synonymous_variant	4/13		XP_047296349.1
BPI	XM_047440394.1 linkuse as main transcript	c.546G>C	p.Val182=	splice_region_variant, synonymous_variant	4/12		XP_047296350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
BPI	ENST00000642449.2 linkuse as main transcript	c.534G>C	p.Val178=	splice_region_variant, synonymous_variant	4/15		NM_001725.3	ENSP00000494528	P1
BPI	ENST00000262865.9 linkuse as main transcript	c.546G>C	p.Val182=	splice_region_variant, synonymous_variant	4/15	1		ENSP00000262865
	ENST00000437016.1 linkuse as main transcript	n.183+15704C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0857

AC:

13032

AN:

152078

Hom.:

755

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0216

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.0942

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0523

Gnomad FIN

AF:

0.102

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.117

Gnomad OTH

AF:

0.0853

GnomAD3 exomes

AF:

0.0936

AC:

23435

AN:

250258

Hom.:

1321

AF XY:

0.0928

AC XY:

12550

AN XY:

135194

show subpopulations

Gnomad AFR exome

AF:

0.0186

Gnomad AMR exome

AF:

0.144

Gnomad ASJ exome

AF:

0.0926

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0501

Gnomad FIN exome

AF:

0.0964

Gnomad NFE exome

AF:

0.115

Gnomad OTH exome

AF:

0.102

GnomAD4 exome

AF:

0.106

AC:

154437

AN:

1459512

Hom.:

8961

Cov.:

AF XY:

0.105

AC XY:

75864

AN XY:

725564

show subpopulations

Gnomad4 AFR exome

AF:

0.0166

Gnomad4 AMR exome

AF:

0.144

Gnomad4 ASJ exome

AF:

0.0910

Gnomad4 EAS exome

AF:

0.000177

Gnomad4 SAS exome

AF:

0.0514

Gnomad4 FIN exome

AF:

0.105

Gnomad4 NFE exome

AF:

0.116

Gnomad4 OTH exome

AF:

0.0910

GnomAD4 genome

AF:

0.0856

AC:

13031

AN:

152196

Hom.:

756

Cov.:

AF XY:

0.0845

AC XY:

6288

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0215

Gnomad4 AMR

AF:

0.140

Gnomad4 ASJ

AF:

0.0942

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0528

Gnomad4 FIN

AF:

0.102

Gnomad4 NFE

AF:

0.117

Gnomad4 OTH

AF:

0.0840

Alfa

AF:

0.108

Hom.:

322

Bravo

AF:

0.0841

Asia WGS

AF:

0.0280

AC:

AN:

3478

EpiCase

AF:

0.102

EpiControl

AF:

0.106

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

BayesDel_noAF

Benign

-0.52

CADD

Benign

3.1

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00043

dbscSNV1_RF

Benign

0.018

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