5-96978798-T-G

Variant names:

• chr5-96978798-T-G
• rs2113050
• NM_005575.3:c.20-340T>G

Variant summary

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

The NM_005575.3(LNPEP):​c.20-340T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 151,978 control chromosomes in the GnomAD database, including 19,013 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 0.50 (19013 hom., cov: 32)
• Consequence: LNPEP NM_005575.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.570
• Publications: 8 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LNPEP	NM_005575.3	c.20-340T>G		intron_variant	Intron 1 of 17	ENST00000231368.10	NP_005566.2
LNPEP	NM_175920.4	c.-23-340T>G		intron_variant	Intron 1 of 17		NP_787116.2
LNPEP	XM_047417177.1	c.20-340T>G		intron_variant	Intron 1 of 15		XP_047273133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LNPEP	ENST00000231368.10	c.20-340T>G		intron_variant	Intron 1 of 17	1	NM_005575.3	ENSP00000231368.5
LNPEP	ENST00000395770.3	c.-23-340T>G		intron_variant	Intron 1 of 17	1		ENSP00000379117.3

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75504 AN: 151860 Hom.: 18970 Cov.: 32

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.498 AC: 75611 AN: 151978 Hom.: 19013 Cov.: 32 AF XY: 0.495 AC XY: 36747 AN XY: 74274

African (AFR) AF: 0.569 AC: 23573 AN: 41432

American (AMR) AF: 0.428 AC: 6524 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1282 AN: 3468

East Asian (EAS) AF: 0.444 AC: 2296 AN: 5166

South Asian (SAS) AF: 0.437 AC: 2107 AN: 4820

European-Finnish (FIN) AF: 0.470 AC: 4962 AN: 10568

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33249 AN: 67960

Other (OTH) AF: 0.486 AC: 1021 AN: 2102

Alfa AF: 0.502 Hom.: 2467

Bravo AF: 0.494

Asia WGS AF: 0.530 AC: 1842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.51
PhyloP100		-0.57
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: rs2113050; hg19: chr5-96314502;