17-58267082-T-C

Variant names:

• chr17-58267082-T-C
• rs8178406
• NM_006151.3:c.1694-267T>C

Variant summary

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

The NM_006151.3(LPO):​c.1694-267T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 152,182 control chromosomes in the GnomAD database, including 20,894 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 (20894 hom., cov: 33)
• Consequence: LPO NM_006151.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.590

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 = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPO	NM_006151.3	c.1694-267T>C		intron_variant	Intron 11 of 12	ENST00000262290.9	NP_006142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPO	ENST00000262290.9	c.1694-267T>C		intron_variant	Intron 11 of 12	1	NM_006151.3	ENSP00000262290.4

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74625 AN: 152064 Hom.: 20839 Cov.: 33

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.457

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: 0.448

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

GnomAD4 genome AF: 0.491 AC: 74741 AN: 152182 Hom.: 20894 Cov.: 33 AF XY: 0.487 AC XY: 36264 AN XY: 74396

Gnomad4 AFR AF: 0.776

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.446

Alfa AF: 0.464 Hom.: 2466

Bravo AF: 0.493

Asia WGS AF: 0.335 AC: 1164 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	0.74
DANN	Benign	0.57

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: rs8178406; hg19: chr17-56344443;