chr20-38304274-G-C

Variant names:

• chr20-38304274-G-C
• rs1341024
• NM_001725.3:c.51G>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.51G>C​(p.Leu17Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 1,613,722 control chromosomes in the GnomAD database, including 226,407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (16331 hom., cov: 32)
  • Exomes 𝑓: 0.53 (210076 hom.)
• Consequence: BPI NM_001725.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.566
• Publications: 16 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=-0.66).
• BP6: Variant 20-38304274-G-C is Benign according to our data. Variant chr20-38304274-G-C is described in ClinVar as Benign. ClinVar VariationId is 402431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.566 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001725.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPI	NM_001725.3	MANE Select	c.51G>C	p.Leu17Leu	synonymous	Exon 1 of 15	NP_001716.3	A0A2R8YDF1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPI	ENST00000642449.2	MANE Select	c.51G>C	p.Leu17Leu	synonymous	Exon 1 of 15	ENSP00000494528.2	A0A2R8YDF1
	BPI	ENST00000262865.10	TSL:1	c.51G>C	p.Leu17Leu	synonymous	Exon 4 of 16	ENSP00000262865.5	P17213
	BPI	ENST00000716802.1		c.51G>C	p.Leu17Leu	synonymous	Exon 3 of 17	ENSP00000520600.1	A0A2R8YDF1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66790 AN: 151934 Hom.: 16319 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.501

GnomAD2 exomes AF: 0.514 AC: 128765 AN: 250652 AF XY: 0.517

Gnomad AFR exome AF: 0.205

Gnomad AMR exome AF: 0.562

Gnomad ASJ exome AF: 0.648

Gnomad EAS exome AF: 0.553

Gnomad FIN exome AF: 0.444

Gnomad NFE exome AF: 0.540

Gnomad OTH exome AF: 0.550

GnomAD4 exome AF: 0.532 AC: 777907 AN: 1461670 Hom.: 210076 Cov.: 66 AF XY: 0.531 AC XY: 386446 AN XY: 727140

African (AFR) AF: 0.206 AC: 6898 AN: 33478

American (AMR) AF: 0.556 AC: 24845 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 17120 AN: 26132

East Asian (EAS) AF: 0.610 AC: 24221 AN: 39692

South Asian (SAS) AF: 0.501 AC: 43188 AN: 86244

European-Finnish (FIN) AF: 0.446 AC: 23826 AN: 53374

Middle Eastern (MID) AF: 0.566 AC: 3264 AN: 5766

European-Non Finnish (NFE) AF: 0.542 AC: 602982 AN: 1111894

Other (OTH) AF: 0.523 AC: 31563 AN: 60386

GnomAD4 genome AF: 0.440 AC: 66837 AN: 152052 Hom.: 16331 Cov.: 32 AF XY: 0.439 AC XY: 32598 AN XY: 74328

African (AFR) AF: 0.218 AC: 9064 AN: 41512

American (AMR) AF: 0.509 AC: 7774 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2197 AN: 3470

East Asian (EAS) AF: 0.569 AC: 2926 AN: 5142

South Asian (SAS) AF: 0.483 AC: 2327 AN: 4818

European-Finnish (FIN) AF: 0.432 AC: 4569 AN: 10580

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36217 AN: 67932

Other (OTH) AF: 0.507 AC: 1071 AN: 2114

Alfa AF: 0.523 Hom.: 12463

Bravo AF: 0.442

Asia WGS AF: 0.543 AC: 1891 AN: 3478

EpiCase AF: 0.562

EpiControl AF: 0.563

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.7
DANN	Benign	0.58
PhyloP100		0.57
PromoterAI		-0.0092	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1341024; hg19: chr20-36932676; COSMIC: COSV53405876;