rs7713127

Positions:

• chr5-96952434-A-G
• chr5-96952434-A-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
LNPEP	NM_005575.3	c.19+16260A>G		intron_variant		ENST00000231368.10	NP_005566.2
LNPEP	XM_047417177.1	c.19+16260A>G		intron_variant			XP_047273133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LNPEP	ENST00000231368.10	c.19+16260A>G		intron_variant		1	NM_005575.3	ENSP00000231368	P1

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

Gnomad4 AFR AF: 0.558

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.444

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.480

Alfa AF: 0.485 Hom.: 5526

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs7713127; hg19: chr5-96288138; COSMIC: COSV51480947;