rs2001209

Variant names:

• chr3-23921155-A-G
• rs2001209
• ENST00000456530.7:c.361-443A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000456530.7(RPL15):​c.361-443A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 152,008 control chromosomes in the GnomAD database, including 13,668 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.39 (13668 hom., cov: 32)
• Consequence: RPL15 ENST00000456530.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 10 publications found

Genes affected

RPL15 (HGNC:10306): (ribosomal protein L15) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of four RNA species and approximately 80 structurally distinct proteins. This gene encodes a member of the L15E family of ribosomal proteins and a component of the 60S subunit. This gene shares sequence similarity with the yeast ribosomal protein YL10 gene. Elevated expression of this gene has been observed in esophageal tumors and gastric cancer tissues, and deletion of this gene has been observed in a Diamond-Blackfan anemia (DBA) patient. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Mar 2017]

NKIRAS1 (HGNC:17899): (NFKB inhibitor interacting Ras like 1) Predicted to enable GTPase activating protein binding activity. Predicted to be involved in I-kappaB kinase/NF-kappaB signaling. Predicted to act upstream of or within several processes, including Ral protein signal transduction; lung alveolus development; and surfactant homeostasis. Located in cytosol and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL15	NM_002948.5	c.*1654A>G		downstream_gene_variant		ENST00000307839.10	NP_002939.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL15	ENST00000456530.7	c.361-443A>G		intron_variant	Intron 4 of 4	1		ENSP00000398788.2
NKIRAS1	ENST00000421515.6	c.-139-9705T>C		intron_variant	Intron 1 of 4	2		ENSP00000392307.2
RPL15	ENST00000307839.10	c.*1654A>G		downstream_gene_variant		1	NM_002948.5	ENSP00000309334.5
RPL15	ENST00000413699.7	c.*1654A>G		downstream_gene_variant		2		ENSP00000416692.1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59325 AN: 151890 Hom.: 13639 Cov.: 32

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.391 AC: 59399 AN: 152008 Hom.: 13668 Cov.: 32 AF XY: 0.389 AC XY: 28952 AN XY: 74346

African (AFR) AF: 0.644 AC: 26683 AN: 41412

American (AMR) AF: 0.395 AC: 6034 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1178 AN: 3468

East Asian (EAS) AF: 0.107 AC: 555 AN: 5172

South Asian (SAS) AF: 0.386 AC: 1865 AN: 4826

European-Finnish (FIN) AF: 0.308 AC: 3258 AN: 10570

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.277 AC: 18857 AN: 67958

Other (OTH) AF: 0.357 AC: 753 AN: 2110

Alfa AF: 0.309 Hom.: 36176

Bravo AF: 0.403

Asia WGS AF: 0.307 AC: 1067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.69
PhyloP100		-1.3
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

Other links and lift over

dbSNP: rs2001209; hg19: chr3-23962646;