rs10044354

Variant names:

• chr5-96984791-C-T
• rs10044354
• NM_005575.3:c.861-289C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005575.3(LNPEP):​c.861-289C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 152,022 control chromosomes in the GnomAD database, including 12,685 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 0.41 (12685 hom., cov: 32)
• Consequence: LNPEP NM_005575.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• Publications: 46 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LNPEP	NM_005575.3	c.861-289C>T		intron_variant	Intron 2 of 17	ENST00000231368.10	NP_005566.2
LNPEP	NM_175920.4	c.819-289C>T		intron_variant	Intron 2 of 17		NP_787116.2
LNPEP	XM_047417177.1	c.861-289C>T		intron_variant	Intron 2 of 15		XP_047273133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LNPEP	ENST00000231368.10	c.861-289C>T		intron_variant	Intron 2 of 17	1	NM_005575.3	ENSP00000231368.5
LNPEP	ENST00000395770.3	c.819-289C>T		intron_variant	Intron 2 of 17	1		ENSP00000379117.3

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61810 AN: 151902 Hom.: 12660 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.407 AC: 61889 AN: 152022 Hom.: 12685 Cov.: 32 AF XY: 0.403 AC XY: 29974 AN XY: 74324

African (AFR) AF: 0.417 AC: 17270 AN: 41434

American (AMR) AF: 0.343 AC: 5239 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1031 AN: 3466

East Asian (EAS) AF: 0.373 AC: 1932 AN: 5180

South Asian (SAS) AF: 0.356 AC: 1716 AN: 4826

European-Finnish (FIN) AF: 0.391 AC: 4127 AN: 10556

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.431 AC: 29303 AN: 67958

Other (OTH) AF: 0.388 AC: 817 AN: 2106

Alfa AF: 0.411 Hom.: 40237

Bravo AF: 0.397

Asia WGS AF: 0.440 AC: 1529 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	1.3
DANN	Benign	0.54
PhyloP100		-0.18
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: rs10044354; hg19: chr5-96320495;