chr16-18788293-C-A

Variant names:

• chr16-18788293-C-A
• rs2641892
• NM_001019.5:c.134-151G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

RPS15A Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Diamond-Blackfan anemia 20

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

ENSG00000260342 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001019.5. 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
	RPS15A	NM_001019.5	MANE Select	c.134-151G>T		intron	N/A	NP_001010.2
	RPS15A	NM_001030009.2		c.134-151G>T		intron	N/A	NP_001025180.1	P62244

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS15A	ENST00000322989.8	TSL:1 MANE Select	c.134-151G>T		intron	N/A	ENSP00000318646.4	P62244
	ENSG00000260342	ENST00000567078.2	TSL:3	c.632-151G>T		intron	N/A	ENSP00000454746.2	H3BN98
	RPS15A	ENST00000563390.5	TSL:1	c.134-151G>T		intron	N/A	ENSP00000457000.1	P62244

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

African (AFR) AF: 0.148 AC: 1819 AN: 12324

American (AMR) AF: 0.0479 AC: 850 AN: 17728

Ashkenazi Jewish (ASJ) AF: 0.0929 AC: 1264 AN: 13600

East Asian (EAS) AF: 0.0000648 AC: 2 AN: 30876

South Asian (SAS) AF: 0.0344 AC: 1547 AN: 45026

European-Finnish (FIN) AF: 0.0504 AC: 1563 AN: 31032

Middle Eastern (MID) AF: 0.0842 AC: 302 AN: 3588

European-Non Finnish (NFE) AF: 0.0705 AC: 19146 AN: 271546

Other (OTH) AF: 0.0689 AC: 1803 AN: 26154

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

African (AFR) AF: 0.152 AC: 6330 AN: 41522

American (AMR) AF: 0.0557 AC: 852 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0910 AC: 316 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.0307 AC: 148 AN: 4824

European-Finnish (FIN) AF: 0.0432 AC: 458 AN: 10608

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0719 AC: 4893 AN: 68016

Other (OTH) AF: 0.0789 AC: 167 AN: 2116

Alfa AF: 0.0756 Hom.: 760

Bravo AF: 0.0906

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.51
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2641892; hg19: chr16-18799615;