rs2953146

Variant names:

• chr2-240575835-G-A
• rs2953146
• NM_018226.6:c.1510+225G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.9).
• 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 rank	MANE	Protein	UniProt
RNPEPL1	NM_018226.6	c.1510+225G>A		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.1510+225G>A		intron_variant	Intron 8 of 10	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

African (AFR) AF: 0.763 AC: 8894 AN: 11656

American (AMR) AF: 0.867 AC: 15130 AN: 17456

Ashkenazi Jewish (ASJ) AF: 0.771 AC: 9682 AN: 12558

East Asian (EAS) AF: 0.960 AC: 27842 AN: 28994

South Asian (SAS) AF: 0.757 AC: 31765 AN: 41960

European-Finnish (FIN) AF: 0.824 AC: 21603 AN: 26202

Middle Eastern (MID) AF: 0.705 AC: 1254 AN: 1778

European-Non Finnish (NFE) AF: 0.796 AC: 192073 AN: 241358

Other (OTH) AF: 0.799 AC: 18889 AN: 23650

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

African (AFR) AF: 0.762 AC: 31660 AN: 41530

American (AMR) AF: 0.835 AC: 12782 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.774 AC: 2687 AN: 3470

East Asian (EAS) AF: 0.960 AC: 4967 AN: 5174

South Asian (SAS) AF: 0.750 AC: 3620 AN: 4826

European-Finnish (FIN) AF: 0.838 AC: 8896 AN: 10614

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.796 AC: 54106 AN: 68010

Other (OTH) AF: 0.793 AC: 1679 AN: 2116

Alfa AF: 0.795 Hom.: 169407

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
PhyloP100		-0.62
PromoterAI		-0.044	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2953146; hg19: chr2-241515252;