chr16-18789316-G-C

Variant names:

• chr16-18789316-G-C
• rs73541341
• NM_001019.5:c.-5-198C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001019.5(RPS15A):​c.-5-198C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0653 in 152,212 control chromosomes in the GnomAD database, including 1,080 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.065 (1080 hom., cov: 32)
• Consequence: RPS15A NM_001019.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.759
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-18789316-G-C is Benign according to our data. Variant chr16-18789316-G-C is described in ClinVar as Benign. ClinVar VariationId is 1290255.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.22 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.-5-198C>G		intron	N/A	NP_001010.2
	RPS15A	NM_001030009.2		c.-5-198C>G		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.-5-198C>G		intron	N/A	ENSP00000318646.4	P62244
	ENSG00000260342	ENST00000567078.2	TSL:3	c.494-198C>G		intron	N/A	ENSP00000454746.2	H3BN98
	RPS15A	ENST00000563390.5	TSL:1	c.-5-198C>G		intron	N/A	ENSP00000457000.1	P62244

Frequencies

GnomAD3 genomes AF: 0.0652 AC: 9915 AN: 152094 Hom.: 1079 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0259

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00147

Gnomad OTH AF: 0.0454

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0653 AC: 9932 AN: 152212 Hom.: 1080 Cov.: 32 AF XY: 0.0630 AC XY: 4690 AN XY: 74424

African (AFR) AF: 0.224 AC: 9307 AN: 41494

American (AMR) AF: 0.0258 AC: 395 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00692 AC: 24 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4816

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10608

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00147 AC: 100 AN: 68026

Other (OTH) AF: 0.0449 AC: 95 AN: 2116

Alfa AF: 0.0544 Hom.: 92

Bravo AF: 0.0755

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.60
DANN	Benign	0.51
PhyloP100		-0.76
PromoterAI		0.045	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs73541341; hg19: chr16-18800638;