Genetic Variant RPL21:n.*371delG (chr13-27256681-TG-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The ENST00000461690.5(RPL21):n.*371delG variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0737 in 637,700 control chromosomes in the GnomAD database, including 2,133 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.096 ( 898 hom., cov: 31)

Exomes 𝑓: 0.067 ( 1235 hom. )

Consequence

RPL21
ENST00000461690.5 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.36

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

hypotrichosis 12
Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
hypotrichosis simplex
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

RPL21 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 13-27256681-TG-T is Benign according to our data. Variant chr13-27256681-TG-T is described in CliVar as Benign. Clinvar id is 1227239.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL21	NM_000982.4 link	c.*157delG		downstream_gene_variant		ENST00000311549.11	NP_000973.2	P46778Q6IAX2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL21	ENST00000311549.11 link	c.*157delG		downstream_gene_variant		1	NM_000982.4	ENSP00000346027.4		P46778

Frequencies

GnomAD3 genomes

AF:

0.0964

AC:

14662

AN:

152172

Hom.:

892

Cov.:

show subpopulations

Gnomad AFR

AF:

0.175

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.0879

Gnomad EAS

AF:

0.0500

Gnomad SAS

AF:

0.0424

Gnomad FIN

AF:

0.0767

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0576

Gnomad OTH

AF:

0.0913

GnomAD4 exome

AF:

0.0666

AC:

32329

AN:

485410

Hom.:

1235

Cov.:

AF XY:

0.0643

AC XY:

16843

AN XY:

262078

show subpopulations

African (AFR)

AF:

0.174

AC:

2228

AN:

12810

American (AMR)

AF:

0.124

AC:

2735

AN:

22096

Ashkenazi Jewish (ASJ)

AF:

0.0848

AC:

1395

AN:

16456

East Asian (EAS)

AF:

0.0648

AC:

2007

AN:

30978

South Asian (SAS)

AF:

0.0481

AC:

2483

AN:

51644

European-Finnish (FIN)

AF:

0.0790

AC:

2402

AN:

30392

Middle Eastern (MID)

AF:

0.0719

AC:

152

AN:

2114

European-Non Finnish (NFE)

AF:

0.0580

AC:

16917

AN:

291514

Other (OTH)

AF:

0.0733

AC:

2010

AN:

27406

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1433

2867

4300

5734

7167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

276

414

552

690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0964

AC:

14685

AN:

152290

Hom.:

898

Cov.:

AF XY:

0.0963

AC XY:

7168

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.175

AC:

7279

AN:

41534

American (AMR)

AF:

0.109

AC:

1665

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0879

AC:

305

AN:

3470

East Asian (EAS)

AF:

0.0495

AC:

257

AN:

5190

South Asian (SAS)

AF:

0.0420

AC:

203

AN:

4832

European-Finnish (FIN)

AF:

0.0767

AC:

814

AN:

10612

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0576

AC:

3921

AN:

68030

Other (OTH)

AF:

0.0903

AC:

191

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

657

1314

1972

2629

3286

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

296

444

592

740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0243

Hom.:

Bravo

AF:

0.104

Asia WGS

AF:

0.0570

AC:

202

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

PhyloP100

-1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over