3-23917732-A-C

Position:

• chr3-23917732-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000354811.5(RPL15):​c.-128A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00229 in 1,043,494 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0096 (26 hom., cov: 33)
  • Exomes 𝑓: 0.0010 (14 hom.)
• Consequence: RPL15 ENST00000354811.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.907

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 3-23917732-A-C is Benign according to our data. Variant chr3-23917732-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1194728.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00958 (1460/152338) while in subpopulation AFR AF= 0.0328 (1365/41560). AF 95% confidence interval is 0.0314. There are 26 homozygotes in gnomad4. There are 721 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1460 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL15	NM_002948.5	c.-10-118A>C		intron_variant		ENST00000307839.10	NP_002939.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL15	ENST00000307839.10	c.-10-118A>C		intron_variant		1	NM_002948.5	ENSP00000309334	P1

Frequencies

GnomAD3 genomes AF: 0.00958 AC: 1458 AN: 152220 Hom.: 26 Cov.: 33

Gnomad AFR AF: 0.0329

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00497

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00716

GnomAD4 exome AF: 0.00104 AC: 929 AN: 891156 Hom.: 14 Cov.: 12 AF XY: 0.000894 AC XY: 402 AN XY: 449428

Gnomad4 AFR exome AF: 0.0354

Gnomad4 AMR exome AF: 0.00317

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000230

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000184

Gnomad4 OTH exome AF: 0.00269

GnomAD4 genome AF: 0.00958 AC: 1460 AN: 152338 Hom.: 26 Cov.: 33 AF XY: 0.00968 AC XY: 721 AN XY: 74496

Gnomad4 AFR AF: 0.0328

Gnomad4 AMR AF: 0.00496

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00709

Alfa AF: 0.00687 Hom.: 3

Bravo AF: 0.0112

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 21, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.8
DANN	Benign	0.83

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: rs116177228; hg19: chr3-23959223;