rs4869317

Variant names:

• chr5-96956300-T-A
• rs4869317
• NM_005575.3:c.19+20126T>A

Variant summary

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

The ENST00000231368.10(LNPEP):​c.19+20126T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,210 control chromosomes in the GnomAD database, including 4,368 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 0.22 (4368 hom., cov: 33)
• Consequence: LNPEP ENST00000231368.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 19 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000231368.10. 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.19+20126T>A		intron	N/A	NP_005566.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LNPEP	ENST00000231368.10	TSL:1 MANE Select	c.19+20126T>A		intron	N/A	ENSP00000231368.5

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34090 AN: 152092 Hom.: 4371 Cov.: 33

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.0313

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.224 AC: 34082 AN: 152210 Hom.: 4368 Cov.: 33 AF XY: 0.222 AC XY: 16556 AN XY: 74416

African (AFR) AF: 0.116 AC: 4806 AN: 41534

American (AMR) AF: 0.245 AC: 3753 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1289 AN: 3470

East Asian (EAS) AF: 0.0312 AC: 162 AN: 5192

South Asian (SAS) AF: 0.275 AC: 1327 AN: 4826

European-Finnish (FIN) AF: 0.265 AC: 2803 AN: 10586

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19081 AN: 67990

Other (OTH) AF: 0.267 AC: 564 AN: 2114

Alfa AF: 0.242 Hom.: 616

Bravo AF: 0.219

Asia WGS AF: 0.131 AC: 461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.58
DANN	Benign	0.77
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4869317; hg19: chr5-96292004;