5-96978798-T-G

Variant summary

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

The NM_005575.3(LNPEP):c.20-340T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 151,978 control chromosomes in the GnomAD database, including 19,013 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 0.50 (19013 hom., cov: 32)
• Consequence: LNPEP NM_005575.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.570

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LNPEP	NM_005575.3	c.20-340T>G		intron_variant		ENST00000231368.10
LNPEP	NM_175920.4	c.-23-340T>G		intron_variant
LNPEP	XM_047417177.1	c.20-340T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LNPEP	ENST00000231368.10	c.20-340T>G		intron_variant		1	NM_005575.3	P1
LNPEP	ENST00000395770.3	c.-23-340T>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75504 AN: 151860 Hom.: 18970 Cov.: 32

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.481

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.498 AC: 75611 AN: 151978 Hom.: 19013 Cov.: 32 AF XY: 0.495 AC XY: 36747 AN XY: 74274

Gnomad4 AFR AF: 0.569

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.444

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.486

Alfa AF: 0.500 Hom.: 2349

Bravo AF: 0.494

Asia WGS AF: 0.530 AC: 1842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.2
Dann	Benign	0.51

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: rs2113050; hg19: chr5-96314502;