2-240576179-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018226.6. 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
	RNPEPL1	NM_018226.6	MANE Select	c.1511-356G>C		intron	N/A	NP_060696.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNPEPL1	ENST00000270357.10	TSL:1 MANE Select	c.1511-356G>C		intron	N/A	ENSP00000270357.4	Q9HAU8
	RNPEPL1	ENST00000471657.1	TSL:1	n.314-356G>C		intron	N/A
	RNPEPL1	ENST00000971323.1		c.1535-356G>C		intron	N/A	ENSP00000641382.1

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

African (AFR) AF: 0.786 AC: 5135 AN: 6536

American (AMR) AF: 0.866 AC: 6294 AN: 7266

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 5036 AN: 6502

East Asian (EAS) AF: 0.961 AC: 12463 AN: 12968

South Asian (SAS) AF: 0.763 AC: 14277 AN: 18706

European-Finnish (FIN) AF: 0.835 AC: 10061 AN: 12042

Middle Eastern (MID) AF: 0.730 AC: 701 AN: 960

European-Non Finnish (NFE) AF: 0.802 AC: 99586 AN: 124190

Other (OTH) AF: 0.809 AC: 10067 AN: 12446

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

African (AFR) AF: 0.780 AC: 32366 AN: 41500

American (AMR) AF: 0.837 AC: 12805 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.774 AC: 2689 AN: 3472

East Asian (EAS) AF: 0.961 AC: 4965 AN: 5166

South Asian (SAS) AF: 0.752 AC: 3633 AN: 4828

European-Finnish (FIN) AF: 0.846 AC: 8966 AN: 10598

Middle Eastern (MID) AF: 0.712 AC: 208 AN: 292

European-Non Finnish (NFE) AF: 0.797 AC: 54223 AN: 68002

Other (OTH) AF: 0.795 AC: 1681 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.70
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2953145; hg19: chr2-241515596;