rs2608830

chr4-39457534-G-Achr4-39457534-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000661.5(RPL9):c.258+52C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 1,405,728 control chromosomes in the GnomAD database, including 24,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2246 hom., cov: 32)
  • Exomes 𝑓: 0.19 (22275 hom.)
• Consequence: RPL9 NM_000661.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.314

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 4-39457534-G-A is Benign according to our data. Variant chr4-39457534-G-A is described in ClinVar as [Benign]. Clinvar id is 1222538.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPL9	NM_000661.5	c.258+52C>T		intron_variant		ENST00000295955.14
RPL9	NM_001024921.4	c.258+52C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL9	ENST00000295955.14	c.258+52C>T		intron_variant		1	NM_000661.5	P1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24194 AN: 151950 Hom.: 2244 Cov.: 32

Gnomad AFR AF: 0.0727

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.185 AC: 232094 AN: 1253660 Hom.: 22275 Cov.: 18 AF XY: 0.185 AC XY: 117527 AN XY: 634376

Gnomad4 AFR exome AF: 0.0741

Gnomad4 AMR exome AF: 0.203

Gnomad4 ASJ exome AF: 0.249

Gnomad4 EAS exome AF: 0.182

Gnomad4 SAS exome AF: 0.175

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.189

GnomAD4 genome AF: 0.159 AC: 24191 AN: 152068 Hom.: 2246 Cov.: 32 AF XY: 0.158 AC XY: 11718 AN XY: 74346

Gnomad4 AFR AF: 0.0725

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.202

Alfa AF: 0.193 Hom.: 4236

Bravo AF: 0.161

Asia WGS AF: 0.176 AC: 614 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	5.9
Dann	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2608830; hg19: chr4-39459154; COSMIC: COSV54695603; COSMIC: COSV54695603;