Genetic Variant RPL26:c.310-49T>G (chr17-8377741-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000987.5(RPL26):c.310-49T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00309 in 1,549,132 control chromosomes in the GnomAD database, including 157 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 12 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 145 hom. )

Consequence

RPL26
NM_000987.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.592

Variant links:

Genes affected

RPL26 (HGNC:10327): (ribosomal protein L26) 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 L24P 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. Mutations in this gene result in Diamond-Blackfan anemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

RPL26 links:

ENSG00000263809 (HGNC:):

ENSG00000263809 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 17-8377741-A-C is Benign according to our data. Variant chr17-8377741-A-C is described in ClinVar as [Benign]. Clinvar id is 1277419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RPL26	NM_000987.5 link	c.310-49T>G	intron_variant	Intron 3 of 3	ENST00000648839.1	NP_000978.1	P61254
RPL26	NM_001315530.2 link	c.310-49T>G	intron_variant	Intron 3 of 3		NP_001302459.1	P61254
RPL26	NM_001315531.2 link	c.310-49T>G	intron_variant	Intron 3 of 3		NP_001302460.1	P61254

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL26	ENST00000648839.1 link	c.310-49T>G		intron_variant	Intron 3 of 3		NM_000987.5	ENSP00000498177.1		P61254
ENSG00000263809	ENST00000582471.1 link	n.310-1637T>G		intron_variant	Intron 3 of 5	5		ENSP00000463847.1		J3QQQ9

Frequencies

GnomAD3 genomes

AF:

0.00354

AC:

538

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0222

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0296

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00336

GnomAD3 exomes

AF:

0.0107

AC:

2393

AN:

223090

Hom.:

AF XY:

0.00836

AC XY:

1021

AN XY:

122172

show subpopulations

Gnomad AFR exome

AF:

0.000544

Gnomad AMR exome

AF:

0.0644

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0318

Gnomad SAS exome

AF:

0.00151

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000380

Gnomad OTH exome

AF:

0.00529

GnomAD4 exome

AF:

0.00305

AC:

4254

AN:

1396830

Hom.:

145

Cov.:

AF XY:

0.00278

AC XY:

1927

AN XY:

692448

show subpopulations

Gnomad4 AFR exome

AF:

0.000540

Gnomad4 AMR exome

AF:

0.0563

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0459

Gnomad4 SAS exome

AF:

0.00163

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000242

Gnomad4 OTH exome

AF:

0.00270

GnomAD4 genome

AF:

0.00353

AC:

537

AN:

152302

Hom.:

Cov.:

AF XY:

0.00393

AC XY:

293

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.0222

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0295

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00181

Hom.:

Bravo

AF:

0.00643

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 21, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.8

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over