16-18788293-C-A

Position:

• chr16-18788293-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001019.5(RPS15A):​c.134-151G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0688 in 604,128 control chromosomes in the GnomAD database, including 1,805 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.087 (695 hom., cov: 32)
  • Exomes 𝑓: 0.063 (1110 hom.)
• Consequence: RPS15A NM_001019.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.213

Genes affected

RPS15A (HGNC:10389): (ribosomal protein S15a) 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 S8P family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-18788293-C-A is Benign according to our data. Variant chr16-18788293-C-A is described in ClinVar as [Benign]. Clinvar id is 1259635.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS15A	NM_001019.5	c.134-151G>T		intron_variant		ENST00000322989.8	NP_001010.2
RPS15A	NM_001030009.2	c.134-151G>T		intron_variant			NP_001025180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS15A	ENST00000322989.8	c.134-151G>T		intron_variant		1	NM_001019.5	ENSP00000318646	P1

Frequencies

GnomAD3 genomes AF: 0.0870 AC: 13241 AN: 152136 Hom.: 694 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0558

Gnomad ASJ AF: 0.0910

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0307

Gnomad FIN AF: 0.0432

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0719

Gnomad OTH AF: 0.0798

GnomAD4 exome AF: 0.0626 AC: 28296 AN: 451874 Hom.: 1110 AF XY: 0.0609 AC XY: 14619 AN XY: 240214

Gnomad4 AFR exome AF: 0.148

Gnomad4 AMR exome AF: 0.0479

Gnomad4 ASJ exome AF: 0.0929

Gnomad4 EAS exome AF: 0.0000648

Gnomad4 SAS exome AF: 0.0344

Gnomad4 FIN exome AF: 0.0504

Gnomad4 NFE exome AF: 0.0705

Gnomad4 OTH exome AF: 0.0689

GnomAD4 genome AF: 0.0870 AC: 13251 AN: 152254 Hom.: 695 Cov.: 32 AF XY: 0.0841 AC XY: 6259 AN XY: 74456

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.0557

Gnomad4 ASJ AF: 0.0910

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0307

Gnomad4 FIN AF: 0.0432

Gnomad4 NFE AF: 0.0719

Gnomad4 OTH AF: 0.0789

Alfa AF: 0.0734 Hom.: 526

Bravo AF: 0.0906

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.51

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: rs2641892; hg19: chr16-18799615;