chr1-201982956-G-T

Variant names:

• chr1-201982956-G-T
• rs549263851
• NM_020216.4:c.290G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001319183.2(RNPEP):​c.-578G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00257 in 1,492,954 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (13 hom.)
• Consequence: RNPEP NM_001319183.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.916
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006571859).
• BS2: High Homozygotes in GnomAdExome4 at 13 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001319183.2. 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
	RNPEP	NM_020216.4	MANE Select	c.290G>T	p.Arg97Leu	missense	Exon 1 of 11	NP_064601.3
	RNPEP	NM_001319183.2		c.-578G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_001306112.1
	RNPEP	NM_001319184.2		c.-432G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_001306113.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNPEP	ENST00000295640.9	TSL:1 MANE Select	c.290G>T	p.Arg97Leu	missense	Exon 1 of 11	ENSP00000295640.4	Q9H4A4
	RNPEP	ENST00000471105.5	TSL:1	n.2G>T		non_coding_transcript_exon	Exon 1 of 10
	RNPEP	ENST00000967255.1		c.290G>T	p.Arg97Leu	missense	Exon 1 of 11	ENSP00000637314.1

Frequencies

GnomAD3 genomes AF: 0.00186 AC: 282 AN: 151956 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00282

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00281

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.00154 AC: 132 AN: 85534 AF XY: 0.00167

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00190

Gnomad ASJ exome AF: 0.000157

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000810

Gnomad NFE exome AF: 0.00273

Gnomad OTH exome AF: 0.00172

GnomAD4 exome AF: 0.00265 AC: 3549 AN: 1340890 Hom.: 13 Cov.: 29 AF XY: 0.00261 AC XY: 1724 AN XY: 660934

African (AFR) AF: 0.000482 AC: 13 AN: 26970

American (AMR) AF: 0.00161 AC: 45 AN: 27898

Ashkenazi Jewish (ASJ) AF: 0.000214 AC: 5 AN: 23378

East Asian (EAS) AF: 0.0000345 AC: 1 AN: 29010

South Asian (SAS) AF: 0.000679 AC: 50 AN: 73618

European-Finnish (FIN) AF: 0.00105 AC: 46 AN: 43964

Middle Eastern (MID) AF: 0.000245 AC: 1 AN: 4088

European-Non Finnish (NFE) AF: 0.00311 AC: 3290 AN: 1056612

Other (OTH) AF: 0.00177 AC: 98 AN: 55352

GnomAD4 genome AF: 0.00185 AC: 282 AN: 152064 Hom.: 0 Cov.: 32 AF XY: 0.00161 AC XY: 120 AN XY: 74326

African (AFR) AF: 0.000698 AC: 29 AN: 41524

American (AMR) AF: 0.00281 AC: 43 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5138

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00281 AC: 191 AN: 67932

Other (OTH) AF: 0.00190 AC: 4 AN: 2110

Alfa AF: 0.00118 Hom.: 0

Bravo AF: 0.00182

ExAC AF: 0.000293 AC: 7

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.79
DANN	Benign	0.91
DEOGEN2	Benign	0.044	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.0066	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.20	N
PhyloP100		-0.92
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.0080
Sift	Benign	0.28	T
Sift4G	Benign	0.31	T
Polyphen		0.0	B
Vest4		0.072
MVP		0.21
MPC		0.19
ClinPred		0.017	T
GERP RS		-2.1
PromoterAI		-0.10	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.054
gMVP		0.35
Mutation Taster		=100/0	polymorphism

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: rs549263851; hg19: chr1-201952084; COSMIC: COSV55240925; COSMIC: COSV55240925;