4-39455015-T-C

Variant names:

• chr4-39455015-T-C
• rs10025155
• NM_000661.5:c.392-71A>G

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.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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.221
• Publications: 3 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 4-39455015-T-C is Benign according to our data. Variant chr4-39455015-T-C is described in ClinVar as Benign. ClinVar VariationId is 1273476.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 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.392-71A>G		intron	N/A	NP_000652.2
	RPL9	NM_001024921.4		c.392-71A>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.392-71A>G		intron	N/A	ENSP00000346022.7	P32969
	RPL9	ENST00000449470.6	TSL:1	c.392-71A>G		intron	N/A	ENSP00000400467.2	P32969
	RPL9	ENST00000503277.6	TSL:2	c.476-71A>G		intron	N/A	ENSP00000494836.1	A0A2R8Y5Y7

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

African (AFR) AF: 0.313 AC: 9006 AN: 28730

American (AMR) AF: 0.159 AC: 5493 AN: 34652

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 5205 AN: 23724

East Asian (EAS) AF: 0.157 AC: 5838 AN: 37132

South Asian (SAS) AF: 0.168 AC: 12878 AN: 76640

European-Finnish (FIN) AF: 0.119 AC: 6128 AN: 51396

Middle Eastern (MID) AF: 0.220 AC: 1186 AN: 5390

European-Non Finnish (NFE) AF: 0.180 AC: 175324 AN: 974890

Other (OTH) AF: 0.195 AC: 10564 AN: 54118

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

African (AFR) AF: 0.307 AC: 12725 AN: 41482

American (AMR) AF: 0.174 AC: 2662 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 753 AN: 3472

East Asian (EAS) AF: 0.164 AC: 847 AN: 5178

South Asian (SAS) AF: 0.152 AC: 733 AN: 4828

European-Finnish (FIN) AF: 0.119 AC: 1263 AN: 10612

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11999 AN: 68008

Other (OTH) AF: 0.207 AC: 439 AN: 2116

Alfa AF: 0.191 Hom.: 1137

Bravo AF: 0.220

Asia WGS AF: 0.158 AC: 549 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	4.0
DANN	Benign	0.62
PhyloP100		0.22
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: rs10025155; hg19: chr4-39456635; COSMIC: COSV54697587; COSMIC: COSV54697587;