dbSNP rs111462631: RPL21:c.243-222A>G (chr13-27255962-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000982.4(RPL21):c.243-222A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00815 in 529,718 control chromosomes in the GnomAD database, including 172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.022 ( 141 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 31 hom. )

Consequence

RPL21
NM_000982.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.884

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 13-27255962-A-G is Benign according to our data. Variant chr13-27255962-A-G is described in ClinVar as [Benign]. Clinvar id is 1233915.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL21	NM_000982.4 link	c.243-222A>G		intron_variant	Intron 4 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.243-222A>G		intron_variant	Intron 4 of 5	1	NM_000982.4	ENSP00000346027.4		P46778

Frequencies

GnomAD3 genomes

AF:

0.0216

AC:

3288

AN:

152200

Hom.:

141

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0750

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00811

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.0172

GnomAD4 exome

AF:

0.00270

AC:

1018

AN:

377400

Hom.:

AF XY:

0.00235

AC XY:

472

AN XY:

200988

show subpopulations

African (AFR)

AF:

0.0704

AC:

748

AN:

10632

American (AMR)

AF:

0.00523

AC:

AN:

15092

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11314

East Asian (EAS)

AF:

0.00

AC:

AN:

23810

South Asian (SAS)

AF:

0.0000988

AC:

AN:

40476

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26032

Middle Eastern (MID)

AF:

0.0100

AC:

AN:

1598

European-Non Finnish (NFE)

AF:

0.000233

AC:

AN:

226998

Other (OTH)

AF:

0.00550

AC:

118

AN:

21448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

126

168

210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0217

AC:

3299

AN:

152318

Hom.:

141

Cov.:

AF XY:

0.0214

AC XY:

1592

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0750

AC:

3118

AN:

41550

American (AMR)

AF:

0.00810

AC:

124

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000220

AC:

AN:

68034

Other (OTH)

AF:

0.0170

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

162

324

486

648

810

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0199

Hom.:

Bravo

AF:

0.0244

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 04, 2019

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

-0.92

CADD

Benign

0.73

(source)

DANN

Benign

0.48

PhyloP100

-0.88

Mutation Taster

=100/0

polymorphism

(source)

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

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rs111462631

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