rs1015450

Variant names:

• chr4-39456237-T-C
• rs1015450
• NM_000661.5:c.391+169A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-39456237-T-C
• chr4-39456237-T-A

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.391+169A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 699,660 control chromosomes in the GnomAD database, including 6,536 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (1214 hom., cov: 34)
  • Exomes 𝑓: 0.13 (5322 hom.)
• Consequence: RPL9 NM_000661.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.112
• 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=-0.85).
• BP6: Variant 4-39456237-T-C is Benign according to our data. Variant chr4-39456237-T-C is described in ClinVar as Benign. ClinVar VariationId is 1289405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.19 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.391+169A>G		intron	N/A	NP_000652.2
	RPL9	NM_001024921.4		c.391+169A>G		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.391+169A>G		intron	N/A	ENSP00000346022.7	P32969
	RPL9	ENST00000449470.6	TSL:1	c.391+169A>G		intron	N/A	ENSP00000400467.2	P32969
	RPL9	ENST00000503277.6	TSL:2	c.475+169A>G		intron	N/A	ENSP00000494836.1	A0A2R8Y5Y7

Frequencies

GnomAD3 genomes AF: 0.161 AC: 18310 AN: 113896 Hom.: 1210 Cov.: 34

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.0913

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.169

GnomAD4 exome AF: 0.130 AC: 76096 AN: 585682 Hom.: 5322 Cov.: 7 AF XY: 0.131 AC XY: 40844 AN XY: 312518

African (AFR) AF: 0.0899 AC: 1385 AN: 15410

American (AMR) AF: 0.102 AC: 3132 AN: 30838

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 2024 AN: 18050

East Asian (EAS) AF: 0.0521 AC: 1614 AN: 30996

South Asian (SAS) AF: 0.133 AC: 7725 AN: 58088

European-Finnish (FIN) AF: 0.107 AC: 4821 AN: 45044

Middle Eastern (MID) AF: 0.107 AC: 421 AN: 3938

European-Non Finnish (NFE) AF: 0.145 AC: 51018 AN: 352476

Other (OTH) AF: 0.128 AC: 3956 AN: 30842

GnomAD4 genome AF: 0.161 AC: 18322 AN: 113978 Hom.: 1214 Cov.: 34 AF XY: 0.159 AC XY: 8762 AN XY: 55184

African (AFR) AF: 0.111 AC: 3776 AN: 33996

American (AMR) AF: 0.171 AC: 1615 AN: 9466

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 371 AN: 2452

East Asian (EAS) AF: 0.111 AC: 369 AN: 3314

South Asian (SAS) AF: 0.192 AC: 548 AN: 2860

European-Finnish (FIN) AF: 0.146 AC: 1156 AN: 7910

Middle Eastern (MID) AF: 0.0877 AC: 20 AN: 228

European-Non Finnish (NFE) AF: 0.193 AC: 9949 AN: 51554

Other (OTH) AF: 0.169 AC: 256 AN: 1518

Alfa AF: 0.133 Hom.: 432

Bravo AF: 0.119

Asia WGS AF: 0.0740 AC: 259 AN: 3462

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	-0.85
CADD	Benign	5.0
DANN	Benign	0.57
PhyloP100		-0.11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs1015450; hg19: chr4-39457857;