rs9127

Positions:

• chr5-97036461-G-A

Variant summary

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

The NM_005575.3(LNPEP):​c.*7928G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 151,918 control chromosomes in the GnomAD database, including 22,394 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 0.54 (22391 hom., cov: 32)
  • Exomes 𝑓: 0.36 (3 hom.)
• Consequence: LNPEP NM_005575.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.754

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LNPEP	NM_005575.3	c.*7928G>A		3_prime_UTR_variant	18/18	ENST00000231368.10
LNPEP	NM_175920.4	c.*7928G>A		3_prime_UTR_variant	18/18
LNPEP	XM_047417177.1	c.*7928G>A		3_prime_UTR_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LNPEP	ENST00000231368.10	c.*7928G>A		3_prime_UTR_variant	18/18	1	NM_005575.3	P1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82083 AN: 151772 Hom.: 22389 Cov.: 32

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.550

GnomAD4 exome AF: 0.357 AC: 10 AN: 28 Hom.: 3 Cov.: 0 AF XY: 0.389 AC XY: 7 AN XY: 18

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.541 AC: 82109 AN: 151890 Hom.: 22391 Cov.: 32 AF XY: 0.546 AC XY: 40552 AN XY: 74224

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.609

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.563

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.545

Alfa AF: 0.548 Hom.: 31520

Bravo AF: 0.544

Asia WGS AF: 0.566 AC: 1968 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	1.3
DANN	Benign	0.69

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: rs9127; hg19: chr5-96372165;