4-39454772-G-A

Variant names:

• chr4-39454772-G-A
• rs1463478
• NM_000661.5:c.472+92C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000661.5(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 NM_000661.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.104
• Publications: 6 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000661.5. 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
	RPL9	NM_000661.5	MANE Select	c.472+92C>T		intron	N/A	NP_000652.2
	RPL9	NM_001024921.4		c.472+92C>T		intron	N/A	NP_001020092.1	Q53Z07

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL9	ENST00000295955.14	TSL:1 MANE Select	c.472+92C>T		intron	N/A	ENSP00000346022.7	P32969
	RPL9	ENST00000449470.6	TSL:1	c.472+92C>T		intron	N/A	ENSP00000400467.2	P32969
	RPL9	ENST00000503277.6	TSL:2	c.556+92C>T		intron	N/A	ENSP00000494836.1	A0A2R8Y5Y7

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

African (AFR) AF: 0.227 AC: 6554 AN: 28826

American (AMR) AF: 0.627 AC: 20065 AN: 32002

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 11357 AN: 23492

East Asian (EAS) AF: 0.571 AC: 21277 AN: 37282

South Asian (SAS) AF: 0.600 AC: 45296 AN: 75516

European-Finnish (FIN) AF: 0.532 AC: 27047 AN: 50816

Middle Eastern (MID) AF: 0.420 AC: 2241 AN: 5338

European-Non Finnish (NFE) AF: 0.515 AC: 517221 AN: 1004614

Other (OTH) AF: 0.491 AC: 26892 AN: 54756

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

African (AFR) AF: 0.243 AC: 10085 AN: 41476

American (AMR) AF: 0.588 AC: 8989 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1710 AN: 3472

East Asian (EAS) AF: 0.573 AC: 2968 AN: 5176

South Asian (SAS) AF: 0.621 AC: 2995 AN: 4826

European-Finnish (FIN) AF: 0.526 AC: 5547 AN: 10548

Middle Eastern (MID) AF: 0.483 AC: 141 AN: 292

European-Non Finnish (NFE) AF: 0.519 AC: 35273 AN: 67972

Other (OTH) AF: 0.484 AC: 1023 AN: 2114

Alfa AF: 0.464 Hom.: 2289

Bravo AF: 0.449

Asia WGS AF: 0.613 AC: 2132 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.8
DANN	Benign	0.65
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

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: rs1463478; hg19: chr4-39456392; COSMIC: COSV107219358; COSMIC: COSV107219358;