rs3756618

Variant names:

• chr5-97029034-T-A
• rs3756618
• ENST00000395770.3:c.*501T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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 (SAS) allele frequency at 95% confidence interval = 0.0809 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000395770.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LNPEP	NM_005575.3	MANE Select	c.*501T>A		3_prime_UTR	Exon 18 of 18	NP_005566.2	Q9UIQ6-1
	LNPEP	NM_175920.4		c.*501T>A		3_prime_UTR	Exon 18 of 18	NP_787116.2	Q9UIQ6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LNPEP	ENST00000395770.3	TSL:1	c.*501T>A		splice_region	Exon 18 of 18	ENSP00000379117.3	Q9UIQ6-2
	LNPEP	ENST00000231368.10	TSL:1 MANE Select	c.*501T>A		3_prime_UTR	Exon 18 of 18	ENSP00000231368.5	Q9UIQ6-1
	LNPEP	ENST00000395770.3	TSL:1	c.*501T>A		3_prime_UTR	Exon 18 of 18	ENSP00000379117.3	Q9UIQ6-2

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

African (AFR) AF: 0.00 AC: 0 AN: 6

American (AMR) AF: 0.00 AC: 0 AN: 30

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00685 AC: 1 AN: 146

South Asian (SAS) AF: 0.300 AC: 3 AN: 10

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00267 AC: 1 AN: 374

Other (OTH) AF: 0.00 AC: 0 AN: 16

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

African (AFR) AF: 0.00123 AC: 51 AN: 41576

American (AMR) AF: 0.00595 AC: 91 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 135 AN: 3472

East Asian (EAS) AF: 0.0640 AC: 332 AN: 5186

South Asian (SAS) AF: 0.0878 AC: 423 AN: 4820

European-Finnish (FIN) AF: 0.0309 AC: 328 AN: 10622

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0115 AC: 783 AN: 68030

Other (OTH) AF: 0.0142 AC: 30 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.49
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3756618;

hg19: chr5-96364738;