19-1438866-C-T

Variant names:

• chr19-1438866-C-T
• rs7251165
• NM_001018.5:c.63C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001018.5(RPS15):​c.63C>T​(p.Asp21Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0519 in 1,590,574 control chromosomes in the GnomAD database, including 2,450 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (258 hom., cov: 32)
  • Exomes 𝑓: 0.052 (2192 hom.)
• Consequence: RPS15 NM_001018.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.251

Genes affected

RPS15 (HGNC:10388): (ribosomal protein S15) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S19P family of ribosomal proteins. It is located in the cytoplasm. This gene has been found to be activated in various tumors, such as insulinomas, esophageal cancers, and colon cancers. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 19-1438866-C-T is Benign according to our data. Variant chr19-1438866-C-T is described in ClinVar as [Benign]. Clinvar id is 440243.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.251 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS15	NM_001018.5	c.63C>T	p.Asp21Asp	synonymous_variant	Exon 2 of 4	ENST00000592588.7	NP_001009.1
RPS15	NM_001308226.2	c.84C>T	p.Asp28Asp	synonymous_variant	Exon 2 of 4		NP_001295155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS15	ENST00000592588.7	c.63C>T	p.Asp21Asp	synonymous_variant	Exon 2 of 4	1	NM_001018.5	ENSP00000467466.3

Frequencies

GnomAD3 genomes AF: 0.0538 AC: 8190 AN: 152170 Hom.: 254 Cov.: 32

Gnomad AFR AF: 0.0483

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0428

Gnomad ASJ AF: 0.0853

Gnomad EAS AF: 0.0358

Gnomad SAS AF: 0.0704

Gnomad FIN AF: 0.0782

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0539

Gnomad OTH AF: 0.0735

GnomAD2 exomes AF: 0.0526 AC: 11189 AN: 212584 AF XY: 0.0551

Gnomad AFR exome AF: 0.0464

Gnomad AMR exome AF: 0.0230

Gnomad ASJ exome AF: 0.0837

Gnomad EAS exome AF: 0.0387

Gnomad FIN exome AF: 0.0779

Gnomad NFE exome AF: 0.0510

Gnomad OTH exome AF: 0.0470

GnomAD4 exome AF: 0.0517 AC: 74306 AN: 1438288 Hom.: 2192 Cov.: 32 AF XY: 0.0530 AC XY: 37822 AN XY: 713588

Gnomad4 AFR exome AF: 0.0455 AC: 1493 AN: 32828

Gnomad4 AMR exome AF: 0.0246 AC: 1051 AN: 42760

Gnomad4 ASJ exome AF: 0.0848 AC: 2180 AN: 25720

Gnomad4 EAS exome AF: 0.0287 AC: 1106 AN: 38506

Gnomad4 SAS exome AF: 0.0767 AC: 6392 AN: 83294

Gnomad4 FIN exome AF: 0.0752 AC: 3805 AN: 50592

Gnomad4 NFE exome AF: 0.0497 AC: 54725 AN: 1101128

Gnomad4 Remaining exome AF: 0.0539 AC: 3196 AN: 59288

GnomAD4 genome AF: 0.0539 AC: 8212 AN: 152286 Hom.: 258 Cov.: 32 AF XY: 0.0558 AC XY: 4152 AN XY: 74466

Gnomad4 AFR AF: 0.0487 AC: 0.0487101 AN: 0.0487101

Gnomad4 AMR AF: 0.0427 AC: 0.0426686 AN: 0.0426686

Gnomad4 ASJ AF: 0.0853 AC: 0.0853026 AN: 0.0853026

Gnomad4 EAS AF: 0.0357 AC: 0.0357281 AN: 0.0357281

Gnomad4 SAS AF: 0.0694 AC: 0.0693869 AN: 0.0693869

Gnomad4 FIN AF: 0.0782 AC: 0.078178 AN: 0.078178

Gnomad4 NFE AF: 0.0539 AC: 0.0538749 AN: 0.0538749

Gnomad4 OTH AF: 0.0761 AC: 0.076087 AN: 0.076087

Alfa AF: 0.0532 Hom.: 204

Bravo AF: 0.0495

Asia WGS AF: 0.0820 AC: 284 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Feb 07, 2017

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	12
DANN	Benign	0.97
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
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

Publications

LitVar

Other links and lift over

dbSNP: rs7251165; hg19: chr19-1438865; COSMIC: COSV51833007; COSMIC: COSV51833007;