5-97016364-C-T

Variant names:

• chr5-97016364-C-T
• rs18059
• NM_005575.3:c.2376+1269C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005575.3(LNPEP):​c.2376+1269C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 151,864 control chromosomes in the GnomAD database, including 20,451 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 0.52 (20451 hom., cov: 31)
• Consequence: LNPEP NM_005575.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.978
• Publications: 23 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LNPEP	NM_005575.3	c.2376+1269C>T		intron_variant	Intron 13 of 17	ENST00000231368.10	NP_005566.2
LNPEP	NM_175920.4	c.2334+1269C>T		intron_variant	Intron 13 of 17		NP_787116.2
LNPEP	XM_047417177.1	c.2376+1269C>T		intron_variant	Intron 13 of 15		XP_047273133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LNPEP	ENST00000231368.10	c.2376+1269C>T		intron_variant	Intron 13 of 17	1	NM_005575.3	ENSP00000231368.5
LNPEP	ENST00000395770.3	c.2334+1269C>T		intron_variant	Intron 13 of 17	1		ENSP00000379117.3

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78357 AN: 151746 Hom.: 20442 Cov.: 31

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.516

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

GnomAD4 genome AF: 0.516 AC: 78396 AN: 151864 Hom.: 20451 Cov.: 31 AF XY: 0.520 AC XY: 38545 AN XY: 74182

African (AFR) AF: 0.549 AC: 22718 AN: 41404

American (AMR) AF: 0.580 AC: 8844 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1867 AN: 3466

East Asian (EAS) AF: 0.624 AC: 3219 AN: 5162

South Asian (SAS) AF: 0.511 AC: 2458 AN: 4806

European-Finnish (FIN) AF: 0.515 AC: 5421 AN: 10534

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32095 AN: 67920

Other (OTH) AF: 0.513 AC: 1081 AN: 2108

Alfa AF: 0.484 Hom.: 12280

Bravo AF: 0.531

Asia WGS AF: 0.510 AC: 1771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.61
DANN	Benign	0.52
PhyloP100		-0.98
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs18059; hg19: chr5-96352068;