rs27290

Positions:

• chr5-97014384-G-A
• chr5-97014384-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LNPEP	NM_005575.3	c.2219+553G>A		intron_variant		ENST00000231368.10	NP_005566.2
LNPEP	NM_175920.4	c.2177+553G>A		intron_variant			NP_787116.2
LNPEP	XM_047417177.1	c.2219+553G>A		intron_variant			XP_047273133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LNPEP	ENST00000231368.10	c.2219+553G>A		intron_variant		1	NM_005575.3	ENSP00000231368.5
LNPEP	ENST00000395770.3	c.2177+553G>A		intron_variant		1		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

Gnomad4 AFR AF: 0.582

Gnomad4 AMR AF: 0.657

Gnomad4 ASJ AF: 0.702

Gnomad4 EAS AF: 0.625

Gnomad4 SAS AF: 0.646

Gnomad4 FIN AF: 0.609

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.612

Alfa AF: 0.587 Hom.: 5000

Bravo AF: 0.603

Asia WGS AF: 0.560 AC: 1949 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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