rs2762

Positions:

• chr5-96937594-C-T

Variant summary

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

The NM_005575.3(LNPEP):​c.19+1420C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 151,808 control chromosomes in the GnomAD database, including 12,503 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 0.40 (12503 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: LNPEP NM_005575.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233

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 = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LNPEP	NM_005575.3	c.19+1420C>T		intron_variant		ENST00000231368.10
LNPEP	XM_047417177.1	c.19+1420C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LNPEP	ENST00000231368.10	c.19+1420C>T		intron_variant		1	NM_005575.3	P1
LNPEP	ENST00000395784.1	n.1903C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61399 AN: 151690 Hom.: 12478 Cov.: 31

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.383

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.405 AC: 61478 AN: 151808 Hom.: 12503 Cov.: 31 AF XY: 0.401 AC XY: 29764 AN XY: 74182

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.374

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.387

Alfa AF: 0.421 Hom.: 2174

Bravo AF: 0.394

Asia WGS AF: 0.439 AC: 1523 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.5
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2762; hg19: chr5-96273298;