Genetic Variant RPL21:c.-12-91C>T (chr13-27253674-C-T) – 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.-12-91C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.912 in 749,288 control chromosomes in the GnomAD database, including 312,404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.88 ( 59198 hom., cov: 34)

Exomes 𝑓: 0.92 ( 253206 hom. )

Consequence

RPL21
NM_000982.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0890

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=-0.87).

BP6

Variant 13-27253674-C-T is Benign according to our data. Variant chr13-27253674-C-T is described in ClinVar as [Benign]. Clinvar id is 1243002.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL21	NM_000982.4 link	c.-12-91C>T		intron_variant	Intron 1 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.-12-91C>T		intron_variant	Intron 1 of 5	1	NM_000982.4	ENSP00000346027.4		P46778

Frequencies

GnomAD3 genomes

AF:

0.879

AC:

133693

AN:

152168

Hom.:

59163

Cov.:

show subpopulations

Gnomad AFR

AF:

0.770

Gnomad AMI

AF:

0.918

Gnomad AMR

AF:

0.855

Gnomad ASJ

AF:

0.908

Gnomad EAS

AF:

0.935

Gnomad SAS

AF:

0.954

Gnomad FIN

AF:

0.936

Gnomad MID

AF:

0.870

Gnomad NFE

AF:

0.929

Gnomad OTH

AF:

0.893

GnomAD4 exome

AF:

0.920

AC:

549281

AN:

597002

Hom.:

253206

Cov.:

AF XY:

0.923

AC XY:

298659

AN XY:

323442

show subpopulations

Gnomad4 AFR exome

AF:

0.770

Gnomad4 AMR exome

AF:

0.841

Gnomad4 ASJ exome

AF:

0.914

Gnomad4 EAS exome

AF:

0.942

Gnomad4 SAS exome

AF:

0.951

Gnomad4 FIN exome

AF:

0.931

Gnomad4 NFE exome

AF:

0.928

Gnomad4 OTH exome

AF:

0.910

GnomAD4 genome

AF:

0.879

AC:

133784

AN:

152286

Hom.:

59198

Cov.:

AF XY:

0.880

AC XY:

65544

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.770

Gnomad4 AMR

AF:

0.855

Gnomad4 ASJ

AF:

0.908

Gnomad4 EAS

AF:

0.936

Gnomad4 SAS

AF:

0.954

Gnomad4 FIN

AF:

0.936

Gnomad4 NFE

AF:

0.929

Gnomad4 OTH

AF:

0.892

Alfa

AF:

0.897

Hom.:

8947

Bravo

AF:

0.865

Asia WGS

AF:

0.922

AC:

3206

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

-0.87

CADD

Benign

4.8

DANN

Benign

0.77

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