4-39452170-A-G

Variant names:

• chr4-39452170-A-G
• rs10517522
• ENST00000894374.1:c.*2373T>C

Variant summary

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

The ENST00000894374.1(RPL9):​c.*2373T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 151,902 control chromosomes in the GnomAD database, including 6,968 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 0.29 (6968 hom., cov: 31)
• Consequence: RPL9 ENST00000894374.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380
• Publications: 19 publications found

Genes affected

RPL9 (HGNC:10369): (ribosomal protein L9) 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 60S subunit. The protein belongs to the L6P 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

RPL9 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000894374.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL9	ENST00000894374.1		c.*2373T>C		3_prime_UTR	Exon 7 of 7	ENSP00000564433.1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43418 AN: 151786 Hom.: 6958 Cov.: 31

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.286 AC: 43439 AN: 151902 Hom.: 6968 Cov.: 31 AF XY: 0.293 AC XY: 21779 AN XY: 74226

African (AFR) AF: 0.136 AC: 5655 AN: 41450

American (AMR) AF: 0.366 AC: 5589 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 828 AN: 3468

East Asian (EAS) AF: 0.394 AC: 2034 AN: 5156

South Asian (SAS) AF: 0.443 AC: 2129 AN: 4806

European-Finnish (FIN) AF: 0.371 AC: 3908 AN: 10524

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22302 AN: 67934

Other (OTH) AF: 0.272 AC: 574 AN: 2112

Alfa AF: 0.315 Hom.: 13590

Bravo AF: 0.276

Asia WGS AF: 0.433 AC: 1506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.1
DANN	Benign	0.60
PhyloP100		0.038

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10517522;

hg19: chr4-39453790;