Variant 1-201989008-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020216.4(RNPEP):c.552G>A(p.Thr184=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00375 in 1,614,064 control chromosomes in the GnomAD database, including 185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 106 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 79 hom. )

Consequence

RNPEP
NM_020216.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.66

Variant links:

Genes affected

RNPEP (HGNC:10078): (arginyl aminopeptidase) Predicted to enable metalloaminopeptidase activity. Predicted to be involved in proteolysis. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

RNPEP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 1-201989008-G-A is Benign according to our data. Variant chr1-201989008-G-A is described in ClinVar as [Benign]. Clinvar id is 767743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RNPEP	NM_020216.4 linkuse as main transcript	c.552G>A	p.Thr184=	synonymous_variant	2/11	ENST00000295640.9	NP_064601.3
RNPEP	NM_001319182.2 linkuse as main transcript	c.159G>A	p.Thr53=	synonymous_variant	2/11		NP_001306111.1
RNPEP	NM_001319183.2 linkuse as main transcript	c.-316G>A		5_prime_UTR_variant	2/10		NP_001306112.1
RNPEP	NM_001319184.2 linkuse as main transcript	c.-170G>A		5_prime_UTR_variant	2/10		NP_001306113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNPEP	ENST00000295640.9 linkuse as main transcript	c.552G>A	p.Thr184=	synonymous_variant	2/11	1	NM_020216.4	ENSP00000295640	P1

Frequencies

GnomAD3 genomes

AF:

0.0199

AC:

3026

AN:

152122

Hom.:

105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0690

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00786

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.0144

GnomAD3 exomes

AF:

0.00524

AC:

1317

AN:

251370

Hom.:

AF XY:

0.00371

AC XY:

504

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.0709

Gnomad AMR exome

AF:

0.00344

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00207

AC:

3019

AN:

1461824

Hom.:

Cov.:

AF XY:

0.00173

AC XY:

1259

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.0709

Gnomad4 AMR exome

AF:

0.00398

Gnomad4 ASJ exome

AF:

0.00161

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000863

Gnomad4 OTH exome

AF:

0.00488

GnomAD4 genome

AF:

0.0199

AC:

3030

AN:

152240

Hom.:

106

Cov.:

AF XY:

0.0192

AC XY:

1426

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0689

Gnomad4 AMR

AF:

0.00785

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.00786

Hom.:

Bravo

AF:

0.0229

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

2.6

DANN

Benign

0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over