rs79818663

chr5-97029127-G-T

Variant summary

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

The NM_005575.3(LNPEP):c.*594G>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 0.0376 in 152,260 control chromosomes in the GnomAD database, including 185 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 0.038 (185 hom., cov: 32)
  • Exomes 𝑓: 0.070 (0 hom.)
• Consequence: LNPEP NM_005575.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LNPEP	NM_005575.3	c.*594G>T		3_prime_UTR_variant	18/18	ENST00000231368.10
LNPEP	NM_175920.4	c.*594G>T		3_prime_UTR_variant	18/18
LNPEP	XM_047417177.1	c.*594G>T		3_prime_UTR_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LNPEP	ENST00000231368.10	c.*594G>T		3_prime_UTR_variant	18/18	1	NM_005575.3	P1

Frequencies

GnomAD3 genomes AF: 0.0376 AC: 5715 AN: 152000 Hom.: 186 Cov.: 32

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.0456

Gnomad ASJ AF: 0.0705

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0288

Gnomad FIN AF: 0.0186

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0551

Gnomad OTH AF: 0.0574

GnomAD4 exome AF: 0.0704 AC: 10 AN: 142 Hom.: 0 Cov.: 0 AF XY: 0.0769 AC XY: 6 AN XY: 78

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0725

Gnomad4 SAS exome AF: 0.00

GnomAD4 genome AF: 0.0376 AC: 5713 AN: 152118 Hom.: 185 Cov.: 32 AF XY: 0.0358 AC XY: 2659 AN XY: 74364

Gnomad4 AFR AF: 0.0103

Gnomad4 AMR AF: 0.0455

Gnomad4 ASJ AF: 0.0705

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0289

Gnomad4 FIN AF: 0.0186

Gnomad4 NFE AF: 0.0552

Gnomad4 OTH AF: 0.0573

Alfa AF: 0.0472 Hom.: 48

Bravo AF: 0.0392

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.11
Dann	Benign	0.61

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: rs79818663; hg19: chr5-96364831;