rs8067912

Positions:

• chr17-58236543-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
		n.58236543T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPO	ENST00000582328.5	c.-288-1194T>C		intron_variant		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

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.0414

Gnomad4 ASJ AF: 0.0380

Gnomad4 EAS AF: 0.0976

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0518

Gnomad4 NFE AF: 0.0368

Gnomad4 OTH AF: 0.0640

Alfa AF: 0.0597 Hom.: 154

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8067912; hg19: chr17-56313904;