rs5743507

Variant names:

• chr20-38310650-G-C
• rs5743507
• NM_001725.3:c.534G>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001725.3(BPI):​c.534G>C​(p.Val178Val) 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
• Publications: 17 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 -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 VariationId 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 rank	MANE	Protein	UniProt
BPI	NM_001725.3	c.534G>C	p.Val178Val	splice_region_variant, synonymous_variant	Exon 4 of 15	ENST00000642449.2	NP_001716.3
BPI	XM_047440393.1	c.546G>C	p.Val182Val	splice_region_variant, synonymous_variant	Exon 4 of 13		XP_047296349.1
BPI	XM_047440394.1	c.546G>C	p.Val182Val	splice_region_variant, synonymous_variant	Exon 4 of 12		XP_047296350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BPI	ENST00000642449.2	c.534G>C	p.Val178Val	splice_region_variant, synonymous_variant	Exon 4 of 15		NM_001725.3	ENSP00000494528.2

Frequencies

GnomAD3 genomes AF: 0.0857 AC: 13032 AN: 152078 Hom.: 755 Cov.: 32

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

GnomAD2 exomes AF: 0.0936 AC: 23435 AN: 250258 AF XY: 0.0928

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 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.: 31 AF XY: 0.105 AC XY: 75864 AN XY: 725564

African (AFR) AF: 0.0166 AC: 557 AN: 33464

American (AMR) AF: 0.144 AC: 6405 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.0910 AC: 2378 AN: 26124

East Asian (EAS) AF: 0.000177 AC: 7 AN: 39630

South Asian (SAS) AF: 0.0514 AC: 4425 AN: 86086

European-Finnish (FIN) AF: 0.105 AC: 5618 AN: 53402

Middle Eastern (MID) AF: 0.0496 AC: 286 AN: 5764

European-Non Finnish (NFE) AF: 0.116 AC: 129271 AN: 1110118

Other (OTH) AF: 0.0910 AC: 5490 AN: 60302

GnomAD4 genome AF: 0.0856 AC: 13031 AN: 152196 Hom.: 756 Cov.: 32 AF XY: 0.0845 AC XY: 6288 AN XY: 74416

African (AFR) AF: 0.0215 AC: 895 AN: 41544

American (AMR) AF: 0.140 AC: 2138 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0942 AC: 327 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5174

South Asian (SAS) AF: 0.0528 AC: 254 AN: 4814

European-Finnish (FIN) AF: 0.102 AC: 1077 AN: 10596

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7925 AN: 67996

Other (OTH) AF: 0.0840 AC: 177 AN: 2108

Alfa AF: 0.108 Hom.: 322

Bravo AF: 0.0841

Asia WGS AF: 0.0280 AC: 99 AN: 3478

EpiCase AF: 0.102

EpiControl AF: 0.106

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: Frequency -

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
BayesDel_noAF	Benign	-0.52
CADD	Benign	3.1
DANN	Benign	0.60
PhyloP100		0.41
Mutation Taster		=69/31	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5743507; hg19: chr20-36939052; COSMIC: COSV53405715;