rs2001209

Positions:

• chr3-23921155-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377380.1(NKIRAS1):​c.-139-9705T>C 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: NKIRAS1 NM_001377380.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NKIRAS1	NM_001377380.1	c.-139-9705T>C		intron_variant			NP_001364309.1
RPL15	NM_001253384.2	c.361-443A>G		intron_variant			NP_001240313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL15	ENST00000456530.7	c.361-443A>G		intron_variant		1		ENSP00000398788.2
NKIRAS1	ENST00000421515.6	c.-139-9705T>C		intron_variant		2		ENSP00000392307.2

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

Gnomad4 AFR AF: 0.644

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.357

Alfa AF: 0.292 Hom.: 14033

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

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: rs2001209; hg19: chr3-23962646;