chr3-23917732-A-C

Variant names:

• chr3-23917732-A-C
• rs116177228
• ENST00000354811.5:c.-128A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001253380.2(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 NM_001253380.2 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.907
• Publications: 1 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1460 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001253380.2. 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
	RPL15	NM_002948.5	MANE Select	c.-10-118A>C		intron	N/A	NP_002939.2
	RPL15	NM_001253380.2		c.-128A>C		5_prime_UTR	Exon 1 of 3	NP_001240309.1	P61313-1
	RPL15	NM_001253379.2		c.-23-105A>C		intron	N/A	NP_001240308.1	P61313-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL15	ENST00000354811.5	TSL:1	c.-128A>C		5_prime_UTR	Exon 1 of 3	ENSP00000346867.5	P61313-1
	RPL15	ENST00000307839.10	TSL:1 MANE Select	c.-10-118A>C		intron	N/A	ENSP00000309334.5	P61313-1
	RPL15	ENST00000456530.7	TSL:1	c.-10-118A>C		intron	N/A	ENSP00000398788.2	P61313-2

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

African (AFR) AF: 0.0354 AC: 723 AN: 20426

American (AMR) AF: 0.00317 AC: 67 AN: 21106

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16518

East Asian (EAS) AF: 0.00 AC: 0 AN: 33662

South Asian (SAS) AF: 0.000230 AC: 13 AN: 56496

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46106

Middle Eastern (MID) AF: 0.00178 AC: 5 AN: 2806

European-Non Finnish (NFE) AF: 0.0000184 AC: 12 AN: 653546

Other (OTH) AF: 0.00269 AC: 109 AN: 40490

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

African (AFR) AF: 0.0328 AC: 1365 AN: 41560

American (AMR) AF: 0.00496 AC: 76 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68034

Other (OTH) AF: 0.00709 AC: 15 AN: 2116

Alfa AF: 0.00836 Hom.: 4

Bravo AF: 0.0112

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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	-0.73
CADD	Benign	3.8
DANN	Benign	0.83
PhyloP100		-0.91
PromoterAI		-0.085	Neutral
Mutation Taster		=300/0	polymorphism

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: rs116177228; hg19: chr3-23959223;