rs2953146

Positions:

• chr2-240575835-G-A
• chr2-240575835-G-T

Variant summary

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

The NM_018226.6(RNPEPL1):​c.1510+225G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 557,860 control chromosomes in the GnomAD database, including 181,324 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 0.80 (48520 hom., cov: 34)
  • Exomes 𝑓: 0.81 (132804 hom.)
• Consequence: RNPEPL1 NM_018226.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.617

Genes affected

RNPEPL1 (HGNC:10079): (arginyl aminopeptidase like 1) Enables metalloaminopeptidase activity. Involved in proteolysis. [provided by Alliance of Genome Resources, Apr 2022]

RNPEPL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNPEPL1	NM_018226.6	c.1510+225G>A		intron_variant		ENST00000270357.10	NP_060696.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNPEPL1	ENST00000270357.10	c.1510+225G>A		intron_variant		1	NM_018226.6	ENSP00000270357.4

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121281 AN: 152130 Hom.: 48477 Cov.: 34

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.854

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.960

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.792

GnomAD4 exome AF: 0.807 AC: 327132 AN: 405612 Hom.: 132804 Cov.: 3 AF XY: 0.804 AC XY: 171098 AN XY: 212796

Gnomad4 AFR exome AF: 0.763

Gnomad4 AMR exome AF: 0.867

Gnomad4 ASJ exome AF: 0.771

Gnomad4 EAS exome AF: 0.960

Gnomad4 SAS exome AF: 0.757

Gnomad4 FIN exome AF: 0.824

Gnomad4 NFE exome AF: 0.796

Gnomad4 OTH exome AF: 0.799

GnomAD4 genome AF: 0.797 AC: 121381 AN: 152248 Hom.: 48520 Cov.: 34 AF XY: 0.801 AC XY: 59588 AN XY: 74436

Gnomad4 AFR AF: 0.762

Gnomad4 AMR AF: 0.835

Gnomad4 ASJ AF: 0.774

Gnomad4 EAS AF: 0.960

Gnomad4 SAS AF: 0.750

Gnomad4 FIN AF: 0.838

Gnomad4 NFE AF: 0.796

Gnomad4 OTH AF: 0.793

Alfa AF: 0.793 Hom.: 58416

Bravo AF: 0.799

Asia WGS AF: 0.848 AC: 2947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.73

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: rs2953146; hg19: chr2-241515252;