rs3756618

Positions:

• chr5-97029034-T-A

Variant summary

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

The ENST00000395770.3(LNPEP):​c.*501T>A variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 152,916 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.014 (52 hom., cov: 32)
  • Exomes 𝑓: 0.0085 (0 hom.)
• Consequence: LNPEP ENST00000395770.3 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LNPEP	NM_005575.3	c.*501T>A		3_prime_UTR_variant	18/18	ENST00000231368.10	NP_005566.2
LNPEP	NM_175920.4	c.*501T>A		3_prime_UTR_variant	18/18		NP_787116.2
LNPEP	XM_047417177.1	c.*501T>A		3_prime_UTR_variant	16/16		XP_047273133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LNPEP	ENST00000395770.3	c.*501T>A		splice_region_variant	18/18	1		ENSP00000379117.3
LNPEP	ENST00000231368.10	c.*501T>A		3_prime_UTR_variant	18/18	1	NM_005575.3	ENSP00000231368.5
LNPEP	ENST00000395770.3	c.*501T>A		3_prime_UTR_variant	18/18	1		ENSP00000379117.3

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 2180 AN: 152208 Hom.: 52 Cov.: 32

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00595

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.0641

Gnomad SAS AF: 0.0875

Gnomad FIN AF: 0.0309

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0115

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.00847 AC: 5 AN: 590 Hom.: 0 Cov.: 0 AF XY: 0.00617 AC XY: 2 AN XY: 324

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00685

Gnomad4 SAS exome AF: 0.300

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00267

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0143 AC: 2182 AN: 152326 Hom.: 52 Cov.: 32 AF XY: 0.0168 AC XY: 1250 AN XY: 74484

Gnomad4 AFR AF: 0.00123

Gnomad4 AMR AF: 0.00595

Gnomad4 ASJ AF: 0.0389

Gnomad4 EAS AF: 0.0640

Gnomad4 SAS AF: 0.0878

Gnomad4 FIN AF: 0.0309

Gnomad4 NFE AF: 0.0115

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.0167 Hom.: 5

Bravo AF: 0.00964

Asia WGS AF: 0.0700 AC: 241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs3756618; hg19: chr5-96364738;