rs8178409

Variant names:

• chr17-58267506-G-A
• rs8178409
• NM_006151.3:c.1851G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-58267506-G-A
• chr17-58267506-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006151.3(LPO):​c.1851G>A​(p.Pro617Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,614,012 control chromosomes in the GnomAD database, including 34,444 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 0.20 (3042 hom., cov: 32)
  • Exomes 𝑓: 0.20 (31402 hom.)
• Consequence: LPO NM_006151.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 13 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP7: Synonymous conserved (PhyloP=-1.06 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006151.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPO	NM_006151.3	MANE Select	c.1851G>A	p.Pro617Pro	synonymous	Exon 12 of 13	NP_006142.1
	LPO	NM_001160102.2		c.1602G>A	p.Pro534Pro	synonymous	Exon 10 of 11	NP_001153574.1
	LPO	NR_027647.2		n.1921G>A		non_coding_transcript_exon	Exon 11 of 12

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPO	ENST00000262290.9	TSL:1 MANE Select	c.1851G>A	p.Pro617Pro	synonymous	Exon 12 of 13	ENSP00000262290.4
	LPO	ENST00000421678.6	TSL:1	c.1602G>A	p.Pro534Pro	synonymous	Exon 10 of 11	ENSP00000400245.2
	LPO	ENST00000389576.4	TSL:1	n.*776G>A		non_coding_transcript_exon	Exon 6 of 7	ENSP00000374227.4

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29868 AN: 152082 Hom.: 3030 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.177

GnomAD2 exomes AF: 0.198 AC: 49712 AN: 251322 AF XY: 0.200

Gnomad AFR exome AF: 0.189

Gnomad AMR exome AF: 0.143

Gnomad ASJ exome AF: 0.182

Gnomad EAS exome AF: 0.130

Gnomad FIN exome AF: 0.278

Gnomad NFE exome AF: 0.209

Gnomad OTH exome AF: 0.181

GnomAD4 exome AF: 0.204 AC: 297522 AN: 1461812 Hom.: 31402 Cov.: 33 AF XY: 0.203 AC XY: 147862 AN XY: 727218

African (AFR) AF: 0.193 AC: 6473 AN: 33480

American (AMR) AF: 0.142 AC: 6348 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 4844 AN: 26136

East Asian (EAS) AF: 0.128 AC: 5091 AN: 39698

South Asian (SAS) AF: 0.222 AC: 19111 AN: 86252

European-Finnish (FIN) AF: 0.271 AC: 14493 AN: 53414

Middle Eastern (MID) AF: 0.123 AC: 711 AN: 5768

European-Non Finnish (NFE) AF: 0.206 AC: 228983 AN: 1111948

Other (OTH) AF: 0.190 AC: 11468 AN: 60394

GnomAD4 genome AF: 0.197 AC: 29910 AN: 152200 Hom.: 3042 Cov.: 32 AF XY: 0.197 AC XY: 14648 AN XY: 74404

African (AFR) AF: 0.192 AC: 7984 AN: 41548

American (AMR) AF: 0.131 AC: 2001 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 611 AN: 3468

East Asian (EAS) AF: 0.124 AC: 640 AN: 5174

South Asian (SAS) AF: 0.208 AC: 1001 AN: 4822

European-Finnish (FIN) AF: 0.268 AC: 2839 AN: 10584

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14205 AN: 67988

Other (OTH) AF: 0.178 AC: 375 AN: 2112

Alfa AF: 0.200 Hom.: 2898

Bravo AF: 0.185

Asia WGS AF: 0.165 AC: 570 AN: 3478

EpiCase AF: 0.186

EpiControl AF: 0.185

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	11
DANN	Benign	0.82
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8178409; hg19: chr17-56344867; COSMIC: COSV51857271; COSMIC: COSV51857271;