20-38308940-C-T

Position:

• chr20-38308940-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001725.3(BPI):​c.256C>T​(p.Arg86Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000975 in 1,614,134 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00093 (6 hom.)
• Consequence: BPI NM_001725.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.203

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=0.0070115924).
• BP6: Variant 20-38308940-C-T is Benign according to our data. Variant chr20-38308940-C-T is described in ClinVar as [Benign]. Clinvar id is 777548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000927 (1355/1461860) while in subpopulation AMR AF= 0.0184 (823/44724). AF 95% confidence interval is 0.0174. There are 6 homozygotes in gnomad4_exome. There are 656 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPI	NM_001725.3	c.256C>T	p.Arg86Cys	missense_variant	3/15	ENST00000642449.2	NP_001716.3
BPI	XM_047440393.1	c.268C>T	p.Arg90Cys	missense_variant	3/13		XP_047296349.1
BPI	XM_047440394.1	c.268C>T	p.Arg90Cys	missense_variant	3/12		XP_047296350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BPI	ENST00000642449.2	c.256C>T	p.Arg86Cys	missense_variant	3/15		NM_001725.3	ENSP00000494528	P1
BPI	ENST00000262865.9	c.268C>T	p.Arg90Cys	missense_variant	3/15	1		ENSP00000262865
	ENST00000437016.1	n.183+17414G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00143 AC: 218 AN: 152156 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00282 AC: 710 AN: 251438 Hom.: 3 AF XY: 0.00235 AC XY: 319 AN XY: 135886

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0175

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00288

Gnomad SAS exome AF: 0.000359

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.000237

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.000927 AC: 1355 AN: 1461860 Hom.: 6 Cov.: 31 AF XY: 0.000902 AC XY: 656 AN XY: 727236

Gnomad4 AFR exome AF: 0.000119

Gnomad4 AMR exome AF: 0.0184

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00559

Gnomad4 SAS exome AF: 0.000348

Gnomad4 FIN exome AF: 0.000131

Gnomad4 NFE exome AF: 0.000207

Gnomad4 OTH exome AF: 0.000646

GnomAD4 genome AF: 0.00143 AC: 218 AN: 152274 Hom.: 0 Cov.: 33 AF XY: 0.00169 AC XY: 126 AN XY: 74458

Gnomad4 AFR AF: 0.000168

Gnomad4 AMR AF: 0.0115

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00367

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000683 Hom.: 1

Bravo AF: 0.00203

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.00217 AC: 264

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	Jul 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.072	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.77	T
MetaRNN	Benign	0.0070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.049
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.012	D
Polyphen		0.97	D
Vest4		0.39
MVP		0.22
MPC		0.19
ClinPred		0.10	T
GERP RS		0.90
Varity_R		0.21
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs5743500; hg19: chr20-36937342; COSMIC: COSV53403969; COSMIC: COSV53403969;