rs2608830

Variant names:

• chr4-39457534-G-A
• rs2608830
• NM_000661.5:c.258+52C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-39457534-G-A
• chr4-39457534-G-C

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.258+52C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 1,405,728 control chromosomes in the GnomAD database, including 24,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2246 hom., cov: 32)
  • Exomes 𝑓: 0.19 (22275 hom.)
• Consequence: RPL9 NM_000661.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.314
• Publications: 12 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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 4-39457534-G-A is Benign according to our data. Variant chr4-39457534-G-A is described in ClinVar as Benign. ClinVar VariationId is 1222538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL9	NM_000661.5	c.258+52C>T		intron_variant	Intron 4 of 7	ENST00000295955.14	NP_000652.2
RPL9	NM_001024921.4	c.258+52C>T		intron_variant	Intron 4 of 7		NP_001020092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL9	ENST00000295955.14	c.258+52C>T		intron_variant	Intron 4 of 7	1	NM_000661.5	ENSP00000346022.7

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24194 AN: 151950 Hom.: 2244 Cov.: 32

Gnomad AFR AF: 0.0727

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.185 AC: 232094 AN: 1253660 Hom.: 22275 Cov.: 18 AF XY: 0.185 AC XY: 117527 AN XY: 634376

African (AFR) AF: 0.0741 AC: 2188 AN: 29524

American (AMR) AF: 0.203 AC: 8997 AN: 44372

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 6169 AN: 24796

East Asian (EAS) AF: 0.182 AC: 7062 AN: 38780

South Asian (SAS) AF: 0.175 AC: 14325 AN: 81984

European-Finnish (FIN) AF: 0.162 AC: 8597 AN: 53138

Middle Eastern (MID) AF: 0.209 AC: 894 AN: 4280

European-Non Finnish (NFE) AF: 0.188 AC: 173776 AN: 923358

Other (OTH) AF: 0.189 AC: 10086 AN: 53428

GnomAD4 genome AF: 0.159 AC: 24191 AN: 152068 Hom.: 2246 Cov.: 32 AF XY: 0.158 AC XY: 11718 AN XY: 74346

African (AFR) AF: 0.0725 AC: 3009 AN: 41476

American (AMR) AF: 0.217 AC: 3314 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 880 AN: 3470

East Asian (EAS) AF: 0.178 AC: 923 AN: 5188

South Asian (SAS) AF: 0.177 AC: 852 AN: 4826

European-Finnish (FIN) AF: 0.155 AC: 1640 AN: 10564

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12933 AN: 67964

Other (OTH) AF: 0.202 AC: 425 AN: 2106

Alfa AF: 0.189 Hom.: 5631

Bravo AF: 0.161

Asia WGS AF: 0.176 AC: 614 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.9
DANN	Benign	0.74
PhyloP100		-0.31
PromoterAI		0.054	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2608830; hg19: chr4-39459154; COSMIC: COSV54695603; COSMIC: COSV54695603;