chr5-96954943-C-T

Position:

• chr5-96954943-C-T

Variant summary

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

The NM_005575.3(LNPEP):​c.19+18769C>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 148,430 control chromosomes in the GnomAD database, including 12,354 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 (12354 hom., cov: 25)
• Consequence: LNPEP NM_005575.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52

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=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LNPEP	NM_005575.3	c.19+18769C>T		intron_variant		ENST00000231368.10	NP_005566.2
LNPEP	XM_047417177.1	c.19+18769C>T		intron_variant			XP_047273133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LNPEP	ENST00000231368.10	c.19+18769C>T		intron_variant		1	NM_005575.3	ENSP00000231368.5

Frequencies

GnomAD3 genomes AF: 0.406 AC: 60271 AN: 148318 Hom.: 12330 Cov.: 25

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.383

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

GnomAD4 genome AF: 0.407 AC: 60350 AN: 148430 Hom.: 12354 Cov.: 25 AF XY: 0.402 AC XY: 29070 AN XY: 72276

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.388

Alfa AF: 0.265 Hom.: 580

Bravo AF: 0.397

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.80

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: rs7705093; hg19: chr5-96290647;