1-218331057-GC-G

Position:

• chr1-218331057-GC-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_016052.4(RRP15):​c.816del​(p.Ser272ArgfsTer15) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00446 in 1,612,776 control chromosomes in the GnomAD database, including 40 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0046 (36 hom.)
• Consequence: RRP15 NM_016052.4 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.474

Genes affected

RRP15 (HGNC:24255): (ribosomal RNA processing 15 homolog) This gene encodes a protein that co-purifies with human nucleoli. A similar protein in budding yeast is a component of pre-60S ribosomal particles, and is required for the early maturation steps of the 60S subunit. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 1-218331057-GC-G is Benign according to our data. Variant chr1-218331057-GC-G is described in ClinVar as [Benign]. Clinvar id is 709022.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RRP15	NM_016052.4	c.816del	p.Ser272ArgfsTer15	frameshift_variant	5/5	ENST00000366932.4
RRP15	XM_047421798.1	c.825del	p.Ser275ArgfsTer15	frameshift_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RRP15	ENST00000366932.4	c.816del	p.Ser272ArgfsTer15	frameshift_variant	5/5	1	NM_016052.4	P1

Frequencies

GnomAD3 genomes AF: 0.00317 AC: 482 AN: 152182 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000676

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00426

Gnomad OTH AF: 0.00525

GnomAD3 exomes AF: 0.00480 AC: 1206 AN: 251272 Hom.: 9 AF XY: 0.00574 AC XY: 779 AN XY: 135810

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.00127

Gnomad ASJ exome AF: 0.0121

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0148

Gnomad FIN exome AF: 0.000416

Gnomad NFE exome AF: 0.00479

Gnomad OTH exome AF: 0.00440

GnomAD4 exome AF: 0.00460 AC: 6718 AN: 1460476 Hom.: 36 Cov.: 30 AF XY: 0.00497 AC XY: 3610 AN XY: 726598

Gnomad4 AFR exome AF: 0.000598

Gnomad4 AMR exome AF: 0.00166

Gnomad4 ASJ exome AF: 0.0104

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0153

Gnomad4 FIN exome AF: 0.000618

Gnomad4 NFE exome AF: 0.00415

Gnomad4 OTH exome AF: 0.00532

GnomAD4 genome AF: 0.00316 AC: 481 AN: 152300 Hom.: 4 Cov.: 32 AF XY: 0.00310 AC XY: 231 AN XY: 74468

Gnomad4 AFR AF: 0.000674

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0112

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00426

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00527 Hom.: 0

Bravo AF: 0.00313

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 09, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs541335404; hg19: chr1-218504399; COSMIC: COSV65117252;