rs1057808

Positions:

• chr5-97028941-T-C

Variant summary

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

The NM_005575.3(LNPEP):​c.*408T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 174,162 control chromosomes in the GnomAD database, including 204 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 0.037 (184 hom., cov: 32)
  • Exomes 𝑓: 0.043 (20 hom.)
• Consequence: LNPEP NM_005575.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193

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=-0.86).
• 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	Protein	UniProt
LNPEP	NM_005575.3	c.*408T>C		3_prime_UTR_variant	18/18	ENST00000231368.10	NP_005566.2
LNPEP	NM_175920.4	c.*408T>C		3_prime_UTR_variant	18/18		NP_787116.2
LNPEP	XM_047417177.1	c.*408T>C		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.*408T>C		3_prime_UTR_variant	18/18	1	NM_005575.3	ENSP00000231368	P1
LNPEP	ENST00000395770.3	c.*408T>C		3_prime_UTR_variant	18/18	1		ENSP00000379117

Frequencies

GnomAD3 genomes AF: 0.0374 AC: 5694 AN: 152158 Hom.: 185 Cov.: 32

Gnomad AFR AF: 0.00965

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0457

Gnomad ASJ AF: 0.0704

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0286

Gnomad FIN AF: 0.0185

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0551

Gnomad OTH AF: 0.0566

GnomAD4 exome AF: 0.0427 AC: 935 AN: 21886 Hom.: 20 Cov.: 0 AF XY: 0.0411 AC XY: 453 AN XY: 11034

Gnomad4 AFR exome AF: 0.00505

Gnomad4 AMR exome AF: 0.0469

Gnomad4 ASJ exome AF: 0.0704

Gnomad4 EAS exome AF: 0.0132

Gnomad4 SAS exome AF: 0.0314

Gnomad4 FIN exome AF: 0.0163

Gnomad4 NFE exome AF: 0.0455

Gnomad4 OTH exome AF: 0.0530

GnomAD4 genome AF: 0.0374 AC: 5690 AN: 152276 Hom.: 184 Cov.: 32 AF XY: 0.0356 AC XY: 2648 AN XY: 74448

Gnomad4 AFR AF: 0.00963

Gnomad4 AMR AF: 0.0456

Gnomad4 ASJ AF: 0.0704

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0286

Gnomad4 FIN AF: 0.0185

Gnomad4 NFE AF: 0.0552

Gnomad4 OTH AF: 0.0565

Alfa AF: 0.0561 Hom.: 243

Bravo AF: 0.0389

Asia WGS AF: 0.0130 AC: 44 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1057808; hg19: chr5-96364645;