2-240576179-G-C

Variant names:

• chr2-240576179-G-C
• rs2953145
• NM_018226.6:c.1511-356G>C

Variant summary

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

The NM_018226.6(RNPEPL1):​c.1511-356G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 353,802 control chromosomes in the GnomAD database, including 116,236 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 (49271 hom., cov: 33)
  • Exomes 𝑓: 0.81 (66965 hom.)
• Consequence: RNPEPL1 NM_018226.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNPEPL1	NM_018226.6	c.1511-356G>C		intron_variant	Intron 8 of 10	ENST00000270357.10	NP_060696.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNPEPL1	ENST00000270357.10	c.1511-356G>C		intron_variant	Intron 8 of 10	1	NM_018226.6	ENSP00000270357.4

Frequencies

GnomAD3 genomes AF: 0.804 AC: 122214 AN: 152068 Hom.: 49229 Cov.: 33

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.836

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.961

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.846

Gnomad MID AF: 0.713

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.793

GnomAD4 exome AF: 0.812 AC: 163620 AN: 201616 Hom.: 66965 Cov.: 0 AF XY: 0.809 AC XY: 84603 AN XY: 104580

Gnomad4 AFR exome AF: 0.786

Gnomad4 AMR exome AF: 0.866

Gnomad4 ASJ exome AF: 0.775

Gnomad4 EAS exome AF: 0.961

Gnomad4 SAS exome AF: 0.763

Gnomad4 FIN exome AF: 0.835

Gnomad4 NFE exome AF: 0.802

Gnomad4 OTH exome AF: 0.809

GnomAD4 genome AF: 0.804 AC: 122313 AN: 152186 Hom.: 49271 Cov.: 33 AF XY: 0.807 AC XY: 60024 AN XY: 74392

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.837

Gnomad4 ASJ AF: 0.774

Gnomad4 EAS AF: 0.961

Gnomad4 SAS AF: 0.752

Gnomad4 FIN AF: 0.846

Gnomad4 NFE AF: 0.797

Gnomad4 OTH AF: 0.795

Alfa AF: 0.774 Hom.: 2775

Bravo AF: 0.805

Asia WGS AF: 0.851 AC: 2958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2953145; hg19: chr2-241515596;