4-39454772-G-A

Position:

• chr4-39454772-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000295955.14(RPL9):​c.472+92C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 1,464,710 control chromosomes in the GnomAD database, including 195,461 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (17192 hom., cov: 33)
  • Exomes 𝑓: 0.52 (178269 hom.)
• Consequence: RPL9 ENST00000295955.14 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.104

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 4-39454772-G-A is Benign according to our data. Variant chr4-39454772-G-A is described in ClinVar as [Benign]. Clinvar id is 1264177.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL9	NM_000661.5	c.472+92C>T		intron_variant		ENST00000295955.14	NP_000652.2
RPL9	NM_001024921.4	c.472+92C>T		intron_variant			NP_001020092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL9	ENST00000295955.14	c.472+92C>T		intron_variant		1	NM_000661.5	ENSP00000346022	P1

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69200 AN: 151950 Hom.: 17188 Cov.: 33

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.481

GnomAD4 exome AF: 0.516 AC: 677950 AN: 1312642 Hom.: 178269 Cov.: 19 AF XY: 0.519 AC XY: 339675 AN XY: 654448

Gnomad4 AFR exome AF: 0.227

Gnomad4 AMR exome AF: 0.627

Gnomad4 ASJ exome AF: 0.483

Gnomad4 EAS exome AF: 0.571

Gnomad4 SAS exome AF: 0.600

Gnomad4 FIN exome AF: 0.532

Gnomad4 NFE exome AF: 0.515

Gnomad4 OTH exome AF: 0.491

GnomAD4 genome AF: 0.455 AC: 69230 AN: 152068 Hom.: 17192 Cov.: 33 AF XY: 0.461 AC XY: 34261 AN XY: 74328

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.588

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.573

Gnomad4 SAS AF: 0.621

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.484

Alfa AF: 0.473 Hom.: 2262

Bravo AF: 0.449

Asia WGS AF: 0.613 AC: 2132 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.80
CADD	Benign	4.8
DANN	Benign	0.65

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: rs1463478; hg19: chr4-39456392;