5-97014384-G-A

Variant names:

• chr5-97014384-G-A
• rs27290
• NM_005575.3:c.2219+553G>A

Variant summary

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

The NM_005575.3(LNPEP):​c.2219+553G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 151,928 control chromosomes in the GnomAD database, including 26,776 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 0.59 (26776 hom., cov: 31)
• Consequence: LNPEP NM_005575.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700
• Publications: 34 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005575.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LNPEP	NM_005575.3	MANE Select	c.2219+553G>A		intron	N/A	NP_005566.2
	LNPEP	NM_175920.4		c.2177+553G>A		intron	N/A	NP_787116.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LNPEP	ENST00000231368.10	TSL:1 MANE Select	c.2219+553G>A		intron	N/A	ENSP00000231368.5
	LNPEP	ENST00000395770.3	TSL:1	c.2177+553G>A		intron	N/A	ENSP00000379117.3

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90055 AN: 151810 Hom.: 26772 Cov.: 31

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.616

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

GnomAD4 genome AF: 0.593 AC: 90093 AN: 151928 Hom.: 26776 Cov.: 31 AF XY: 0.597 AC XY: 44306 AN XY: 74254

African (AFR) AF: 0.582 AC: 24108 AN: 41454

American (AMR) AF: 0.657 AC: 10031 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 2434 AN: 3466

East Asian (EAS) AF: 0.625 AC: 3224 AN: 5158

South Asian (SAS) AF: 0.646 AC: 3109 AN: 4816

European-Finnish (FIN) AF: 0.609 AC: 6423 AN: 10548

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38717 AN: 67910

Other (OTH) AF: 0.612 AC: 1291 AN: 2108

Alfa AF: 0.591 Hom.: 9619

Bravo AF: 0.603

Asia WGS AF: 0.560 AC: 1949 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.4
DANN	Benign	0.61
PhyloP100		0.0070
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: rs27290; hg19: chr5-96350088;