rs8178290

Positions:

• chr17-58242797-C-A
• chr17-58242797-C-T

Variant summary

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

The NM_006151.3(LPO):​c.-2-181C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 568,408 control chromosomes in the GnomAD database, including 14,592 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 0.23 (4216 hom., cov: 32)
  • Exomes 𝑓: 0.21 (10376 hom.)
• Consequence: LPO NM_006151.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.818

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPO	NM_006151.3	c.-2-181C>A		intron_variant		ENST00000262290.9
LOC124904038	XR_007065862.1	n.1986G>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPO	ENST00000262290.9	c.-2-181C>A		intron_variant		1	NM_006151.3	P1
	ENST00000655053.1	n.3936G>T		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35110 AN: 151956 Hom.: 4206 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.195

GnomAD4 exome AF: 0.214 AC: 89210 AN: 416334 Hom.: 10376 AF XY: 0.214 AC XY: 47107 AN XY: 220292

Gnomad4 AFR exome AF: 0.271

Gnomad4 AMR exome AF: 0.143

Gnomad4 ASJ exome AF: 0.178

Gnomad4 EAS exome AF: 0.126

Gnomad4 SAS exome AF: 0.227

Gnomad4 FIN exome AF: 0.311

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.231 AC: 35156 AN: 152074 Hom.: 4216 Cov.: 32 AF XY: 0.233 AC XY: 17354 AN XY: 74352

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.196

Alfa AF: 0.206 Hom.: 3288

Bravo AF: 0.218

Asia WGS AF: 0.169 AC: 587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.49

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: rs8178290; hg19: chr17-56320158;