Genetic Variant RPL21:c.67+61A>G (chr13-27253904-A-G) – 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_000982.4(RPL21):c.67+61A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0942 in 967,290 control chromosomes in the GnomAD database, including 4,876 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.095 ( 721 hom., cov: 32)

Exomes 𝑓: 0.094 ( 4155 hom. )

Consequence

RPL21
NM_000982.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.55

Variant links:

Genes affected

RPL21 (HGNC:10313): (ribosomal protein L21) 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 L21E 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. [provided by RefSeq, Jul 2008]

RPL21 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 13-27253904-A-G is Benign according to our data. Variant chr13-27253904-A-G is described in ClinVar as [Benign]. Clinvar id is 1237877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL21	NM_000982.4 link	c.67+61A>G		intron_variant	Intron 2 of 5	ENST00000311549.11	NP_000973.2	P46778Q6IAX2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL21	ENST00000311549.11 link	c.67+61A>G		intron_variant	Intron 2 of 5	1	NM_000982.4	ENSP00000346027.4		P46778

Frequencies

GnomAD3 genomes

AF:

0.0945

AC:

14374

AN:

152164

Hom.:

718

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.0482

Gnomad AMR

AF:

0.0772

Gnomad ASJ

AF:

0.0954

Gnomad EAS

AF:

0.00288

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.0635

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.113

GnomAD4 exome

AF:

0.0941

AC:

76726

AN:

815008

Hom.:

4155

AF XY:

0.0974

AC XY:

42010

AN XY:

431416

show subpopulations

Gnomad4 AFR exome

AF:

0.101

Gnomad4 AMR exome

AF:

0.0501

Gnomad4 ASJ exome

AF:

0.0953

Gnomad4 EAS exome

AF:

0.000354

Gnomad4 SAS exome

AF:

0.133

Gnomad4 FIN exome

AF:

0.0656

Gnomad4 NFE exome

AF:

0.101

Gnomad4 OTH exome

AF:

0.0999

GnomAD4 genome

AF:

0.0945

AC:

14396

AN:

152282

Hom.:

721

Cov.:

AF XY:

0.0935

AC XY:

6959

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.0771

Gnomad4 ASJ

AF:

0.0954

Gnomad4 EAS

AF:

0.00289

Gnomad4 SAS

AF:

0.120

Gnomad4 FIN

AF:

0.0635

Gnomad4 NFE

AF:

0.103

Gnomad4 OTH

AF:

0.112

Alfa

AF:

0.102

Hom.:

1093

Bravo

AF:

0.0941

Asia WGS

AF:

0.0740

AC:

256

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

- -

Jul 14, 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

0.40

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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