rs12054720

Positions:

• chr5-96954020-T-C
• chr5-96954020-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000231368.10(LNPEP):​c.19+17846T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0988 in 152,270 control chromosomes in the GnomAD database, including 1,246 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 0.099 (1246 hom., cov: 31)
• Consequence: LNPEP ENST00000231368.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LNPEP	NM_005575.3	c.19+17846T>C		intron_variant		ENST00000231368.10	NP_005566.2
LNPEP	XM_047417177.1	c.19+17846T>C		intron_variant			XP_047273133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LNPEP	ENST00000231368.10	c.19+17846T>C		intron_variant		1	NM_005575.3	ENSP00000231368	P1

Frequencies

GnomAD3 genomes AF: 0.0990 AC: 15057 AN: 152152 Hom.: 1248 Cov.: 31

Gnomad AFR AF: 0.0723

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.0727

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0737

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.0988 AC: 15051 AN: 152270 Hom.: 1246 Cov.: 31 AF XY: 0.102 AC XY: 7597 AN XY: 74462

Gnomad4 AFR AF: 0.0721

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.0727

Gnomad4 NFE AF: 0.0737

Gnomad4 OTH AF: 0.0988

Alfa AF: 0.0903 Hom.: 170

Bravo AF: 0.108

Asia WGS AF: 0.227 AC: 788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.3
DANN	Benign	0.76

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: rs12054720; hg19: chr5-96289724;