13-27253904-A-G

Variant names:

• chr13-27253904-A-G
• rs10467685
• NM_000982.4:c.67+61A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.55
• Publications: 10 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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	c.67+61A>G		intron_variant	Intron 2 of 5	ENST00000311549.11	NP_000973.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0945 AC: 14374 AN: 152164 Hom.: 718 Cov.: 32

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

African (AFR) AF: 0.101 AC: 2119 AN: 21028

American (AMR) AF: 0.0501 AC: 2188 AN: 43650

Ashkenazi Jewish (ASJ) AF: 0.0953 AC: 2097 AN: 22006

East Asian (EAS) AF: 0.000354 AC: 13 AN: 36742

South Asian (SAS) AF: 0.133 AC: 9679 AN: 73040

European-Finnish (FIN) AF: 0.0656 AC: 3458 AN: 52726

Middle Eastern (MID) AF: 0.160 AC: 725 AN: 4534

European-Non Finnish (NFE) AF: 0.101 AC: 52546 AN: 522222

Other (OTH) AF: 0.0999 AC: 3901 AN: 39060

GnomAD4 genome AF: 0.0945 AC: 14396 AN: 152282 Hom.: 721 Cov.: 32 AF XY: 0.0935 AC XY: 6959 AN XY: 74462

African (AFR) AF: 0.104 AC: 4302 AN: 41538

American (AMR) AF: 0.0771 AC: 1180 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0954 AC: 331 AN: 3468

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5196

South Asian (SAS) AF: 0.120 AC: 581 AN: 4832

European-Finnish (FIN) AF: 0.0635 AC: 674 AN: 10608

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6983 AN: 68020

Other (OTH) AF: 0.112 AC: 236 AN: 2116

Alfa AF: 0.100 Hom.: 1455

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

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
PhyloP100		1.6
PromoterAI		0.051	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10467685; hg19: chr13-27828041;