rs8178407

Positions:

• chr17-58267295-A-G
• chr17-58267295-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006151.3(LPO):​c.1694-54A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 1,404,024 control chromosomes in the GnomAD database, including 123,957 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 0.49 (20827 hom., cov: 33)
  • Exomes 𝑓: 0.40 (103130 hom.)
• Consequence: LPO NM_006151.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPO	NM_006151.3	c.1694-54A>G		intron_variant		ENST00000262290.9	NP_006142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPO	ENST00000262290.9	c.1694-54A>G		intron_variant		1	NM_006151.3	ENSP00000262290	P1

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74522 AN: 152022 Hom.: 20773 Cov.: 33

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.447

GnomAD4 exome AF: 0.396 AC: 496115 AN: 1251884 Hom.: 103130 AF XY: 0.397 AC XY: 249942 AN XY: 630142

Gnomad4 AFR exome AF: 0.797

Gnomad4 AMR exome AF: 0.275

Gnomad4 ASJ exome AF: 0.455

Gnomad4 EAS exome AF: 0.229

Gnomad4 SAS exome AF: 0.434

Gnomad4 FIN exome AF: 0.456

Gnomad4 NFE exome AF: 0.387

Gnomad4 OTH exome AF: 0.408

GnomAD4 genome AF: 0.491 AC: 74637 AN: 152140 Hom.: 20827 Cov.: 33 AF XY: 0.487 AC XY: 36201 AN XY: 74360

Gnomad4 AFR AF: 0.774

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.458

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.445

Alfa AF: 0.392 Hom.: 2669

Bravo AF: 0.493

Asia WGS AF: 0.335 AC: 1162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs8178407; hg19: chr17-56344656; COSMIC: COSV51857520; COSMIC: COSV51857520;