rs17087239

Positions:

• chr5-97028594-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005575.3(LNPEP):​c.*61C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000147 in 1,579,214 control chromosomes in the GnomAD database, including 1 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 0.00068 (1 hom., cov: 33)
  • Exomes 𝑓: 0.000090 (0 hom.)
• Consequence: LNPEP NM_005575.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92

Genes affected

LNPEP (HGNC:6656): (leucyl and cystinyl aminopeptidase) This gene encodes a zinc-dependent aminopeptidase that cleaves vasopressin, oxytocin, lys-bradykinin, met-enkephalin, dynorphin A and other peptide hormones. The protein can be secreted in maternal serum, reside in intracellular vesicles with the insulin-responsive glucose transporter GLUT4, or form a type II integral membrane glycoprotein. The protein catalyzes the final step in the conversion of angiotensinogen to angiotensin IV (AT4) and is also a receptor for AT4. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LNPEP	NM_005575.3	c.*61C>T		3_prime_UTR_variant	18/18	ENST00000231368.10	NP_005566.2
LNPEP	NM_175920.4	c.*61C>T		3_prime_UTR_variant	18/18		NP_787116.2
LNPEP	XM_047417177.1	c.*61C>T		3_prime_UTR_variant	16/16		XP_047273133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LNPEP	ENST00000231368.10	c.*61C>T		3_prime_UTR_variant	18/18	1	NM_005575.3	ENSP00000231368	P1
LNPEP	ENST00000395770.3	c.*61C>T		3_prime_UTR_variant	18/18	1		ENSP00000379117

Frequencies

GnomAD3 genomes AF: 0.000677 AC: 103 AN: 152146 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00225

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.0000897 AC: 128 AN: 1426950 Hom.: 0 Cov.: 25 AF XY: 0.0000986 AC XY: 70 AN XY: 710266

Gnomad4 AFR exome AF: 0.00267

Gnomad4 AMR exome AF: 0.000152

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000143

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000916

Gnomad4 OTH exome AF: 0.000204

GnomAD4 genome AF: 0.000683 AC: 104 AN: 152264 Hom.: 1 Cov.: 33 AF XY: 0.000685 AC XY: 51 AN XY: 74442

Gnomad4 AFR AF: 0.00226

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000767 Hom.: 0

Bravo AF: 0.000756

Asia WGS AF: 0.000578 AC: 2 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	12
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs17087239; hg19: chr5-96364298;