chr5-97002801-C-G

Variant names:

• chr5-97002801-C-G
• rs27307
• NM_005575.3:c.1654-614C>G

Variant summary

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

The NM_005575.3(LNPEP):​c.1654-614C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 152,034 control chromosomes in the GnomAD database, including 33,438 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 0.66 (33438 hom., cov: 31)
• Consequence: LNPEP NM_005575.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213
• Publications: 16 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 (AFR) allele frequency at 95% confidence interval = 0.754 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.1654-614C>G		intron	N/A	NP_005566.2
	LNPEP	NM_175920.4		c.1612-614C>G		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.1654-614C>G		intron	N/A	ENSP00000231368.5
	LNPEP	ENST00000395770.3	TSL:1	c.1612-614C>G		intron	N/A	ENSP00000379117.3
	LNPEP	ENST00000473914.1	TSL:2	n.259-614C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100086 AN: 151916 Hom.: 33402 Cov.: 31

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.659 AC: 100172 AN: 152034 Hom.: 33438 Cov.: 31 AF XY: 0.663 AC XY: 49306 AN XY: 74324

African (AFR) AF: 0.761 AC: 31566 AN: 41456

American (AMR) AF: 0.684 AC: 10446 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 2574 AN: 3470

East Asian (EAS) AF: 0.692 AC: 3581 AN: 5178

South Asian (SAS) AF: 0.735 AC: 3543 AN: 4822

European-Finnish (FIN) AF: 0.642 AC: 6775 AN: 10558

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.582 AC: 39520 AN: 67954

Other (OTH) AF: 0.663 AC: 1399 AN: 2110

Alfa AF: 0.475 Hom.: 1186

Bravo AF: 0.671

Asia WGS AF: 0.646 AC: 2248 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	0.76
DANN	Benign	0.24
PhyloP100		-0.21
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: rs27307; hg19: chr5-96338505;