4-39455015-T-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.392-71A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 1,438,862 control chromosomes in the GnomAD database, including 25,383 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3712 hom., cov: 32)
  • Exomes 𝑓: 0.18 (21671 hom.)
• Consequence: RPL9 NM_000661.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.221

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=-0.8).
• BP6: Variant 4-39455015-T-C is Benign according to our data. Variant chr4-39455015-T-C is described in ClinVar as [Benign]. Clinvar id is 1273476.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPL9	NM_000661.5	c.392-71A>G		intron_variant		ENST00000295955.14
RPL9	NM_001024921.4	c.392-71A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL9	ENST00000295955.14	c.392-71A>G		intron_variant		1	NM_000661.5	P1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31686 AN: 152072 Hom.: 3701 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.180 AC: 231622 AN: 1286672 Hom.: 21671 Cov.: 17 AF XY: 0.180 AC XY: 115732 AN XY: 644264

Gnomad4 AFR exome AF: 0.313

Gnomad4 AMR exome AF: 0.159

Gnomad4 ASJ exome AF: 0.219

Gnomad4 EAS exome AF: 0.157

Gnomad4 SAS exome AF: 0.168

Gnomad4 FIN exome AF: 0.119

Gnomad4 NFE exome AF: 0.180

Gnomad4 OTH exome AF: 0.195

GnomAD4 genome AF: 0.209 AC: 31742 AN: 152190 Hom.: 3712 Cov.: 32 AF XY: 0.203 AC XY: 15127 AN XY: 74396

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.207

Alfa AF: 0.186 Hom.: 870

Bravo AF: 0.220

Asia WGS AF: 0.158 AC: 549 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	4.0
Dann	Benign	0.62

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: rs10025155; hg19: chr4-39456635; COSMIC: COSV54697587; COSMIC: COSV54697587;