rs8067912

Variant names:

• chr17-58236543-T-C
• rs8067912
• ENST00000582328.5:c.-288-1194T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000582328.5(LPO):​c.-288-1194T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0822 in 152,182 control chromosomes in the GnomAD database, including 843 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.082 (843 hom., cov: 32)
• Consequence: LPO ENST00000582328.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272
• Publications: 3 publications found

Genes affected

LPO (HGNC:6678): (lactoperoxidase) This gene encodes a member of the peroxidase family of proteins. The encoded preproprotein is proteolytically processed to generate the mature enzyme. Following its secretion from salivary, mammary, and other mucosal glands, this enzyme catalyzes the generation of the antimicrobial substance hypothiocyanous acid. This gene is present in a gene cluster on chromosome 17. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPO	ENST00000582328.5	c.-288-1194T>C		intron_variant	Intron 1 of 12	5		ENSP00000464636.1

Frequencies

GnomAD3 genomes AF: 0.0820 AC: 12463 AN: 152064 Hom.: 831 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0415

Gnomad ASJ AF: 0.0380

Gnomad EAS AF: 0.0974

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0518

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0368

Gnomad OTH AF: 0.0647

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0822 AC: 12511 AN: 152182 Hom.: 843 Cov.: 32 AF XY: 0.0831 AC XY: 6186 AN XY: 74414

African (AFR) AF: 0.182 AC: 7531 AN: 41486

American (AMR) AF: 0.0414 AC: 633 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0380 AC: 132 AN: 3470

East Asian (EAS) AF: 0.0976 AC: 506 AN: 5184

South Asian (SAS) AF: 0.101 AC: 488 AN: 4818

European-Finnish (FIN) AF: 0.0518 AC: 550 AN: 10610

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0368 AC: 2503 AN: 68006

Other (OTH) AF: 0.0640 AC: 135 AN: 2110

Alfa AF: 0.0593 Hom.: 901

Bravo AF: 0.0864

Asia WGS AF: 0.0960 AC: 333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	10
DANN	Benign	0.75
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8067912; hg19: chr17-56313904;