Genetic Variant RPL27:c.-247C>G (chr17-42998504-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001349922.2(RPL27):c.-247C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 152,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RPL27
NM_001349922.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.312

Publications

3 publications found

Variant links:

Genes affected

RPL27 (HGNC:10328): (ribosomal protein L27) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of four RNA species and approximately 80 structurally distinct proteins. This gene encodes a member of the L27e family of ribosomal proteins and a component of the 60S subunit. A splice site mutation in this gene has been identified in a Diamond-Blackfan anemia (DBA) patient. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Mar 2017]

RPL27 Gene-Disease associations (from GenCC):

Diamond-Blackfan anemia 16
Inheritance: Unknown, AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics

RPL27 links:

LOC124904006 (HGNC:):

LOC124904006 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349922.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPL27	NM_000988.5	MANE Select	c.-3+33C>G	intron	N/A	NP_000979.1	P61353
RPL27	NM_001349922.2		c.-247C>G	5_prime_UTR	Exon 1 of 4	NP_001336851.1	P61353
RPL27	NM_001349921.2		c.-3+89C>G	intron	N/A	NP_001336850.1	P61353

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPL27	ENST00000589913.6	TSL:1	c.-247C>G	5_prime_UTR	Exon 1 of 4	ENSP00000464813.1	P61353
RPL27	ENST00000253788.12	TSL:1 MANE Select	c.-3+33C>G	intron	N/A	ENSP00000253788.5	P61353
RPL27	ENST00000905376.1		c.-31C>G	5_prime_UTR	Exon 1 of 5	ENSP00000575435.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

250444

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

133928

African (AFR)

AF:

0.00

AC:

AN:

5544

American (AMR)

AF:

0.00

AC:

AN:

6968

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7946

East Asian (EAS)

AF:

0.00

AC:

AN:

14260

South Asian (SAS)

AF:

0.00

AC:

AN:

31174

European-Finnish (FIN)

AF:

0.00

AC:

AN:

16074

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1130

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

152878

Other (OTH)

AF:

0.00

AC:

AN:

14470

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152068

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41376

American (AMR)

AF:

0.0000655

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68050

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

4219

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.2

(source)

DANN

Benign

0.67

PhyloP100

-0.31

PromoterAI

0.0092

Neutral

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over