5-96952434-A-G

Variant names:

• chr5-96952434-A-G
• rs7713127
• NM_005575.3:c.19+16260A>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.19+16260A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 152,034 control chromosomes in the GnomAD database, including 18,720 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 0.49 (18720 hom., cov: 32)
• Consequence: LNPEP NM_005575.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280
• Publications: 13 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LNPEP	NM_005575.3	c.19+16260A>G		intron_variant	Intron 1 of 17	ENST00000231368.10	NP_005566.2
LNPEP	XM_047417177.1	c.19+16260A>G		intron_variant	Intron 1 of 15		XP_047273133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LNPEP	ENST00000231368.10	c.19+16260A>G		intron_variant	Intron 1 of 17	1	NM_005575.3	ENSP00000231368.5

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75007 AN: 151916 Hom.: 18677 Cov.: 32

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.494 AC: 75114 AN: 152034 Hom.: 18720 Cov.: 32 AF XY: 0.491 AC XY: 36494 AN XY: 74288

African (AFR) AF: 0.558 AC: 23131 AN: 41462

American (AMR) AF: 0.427 AC: 6527 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1282 AN: 3470

East Asian (EAS) AF: 0.444 AC: 2296 AN: 5174

South Asian (SAS) AF: 0.437 AC: 2105 AN: 4818

European-Finnish (FIN) AF: 0.468 AC: 4947 AN: 10560

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33220 AN: 67960

Other (OTH) AF: 0.480 AC: 1015 AN: 2114

Alfa AF: 0.487 Hom.: 7020

Bravo AF: 0.490

Asia WGS AF: 0.529 AC: 1839 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.1
DANN	Benign	0.61
PhyloP100		0.028
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: rs7713127; hg19: chr5-96288138; COSMIC: COSV51480947;