Genetic Variant RPS27:c.7-8C>T (chr1-153991107-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001030.6(RPS27):c.7-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000332 in 1,558,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

RPS27
NM_001030.6 splice_region, intron

Scores

Splicing: ADA: 0.00008309

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.05

Publications

0 publications found

Variant links:

Genes affected

RPS27 (HGNC:10416): (ribosomal protein S27) 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 S27e family of ribosomal proteins and component of the 40S subunit. The encoded protein contains a C4-type zinc finger domain that can bind to zinc and may bind to nucleic acid. Mutations in this gene have been identified in numerous melanoma patients and in at least one patient with Diamond-Blackfan anemia (DBA). Elevated expression of this gene has been observed in various human cancers. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2018]

RPS27 Gene-Disease associations (from GenCC):

Diamond-Blackfan anemia 17
Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

RPS27 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 1-153991107-C-T is Benign according to our data. Variant chr1-153991107-C-T is described in ClinVar as Benign. ClinVar VariationId is 727666.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 301 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001030.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPS27	NM_001030.6	MANE Select	c.7-8C>T	splice_region intron	N/A	NP_001021.1	P42677
RPS27	NM_001349946.2		c.-90-8C>T	splice_region intron	N/A	NP_001336875.1
RPS27	NM_001349947.2		c.-90-8C>T	splice_region intron	N/A	NP_001336876.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPS27	ENST00000651669.1	MANE Select	c.7-8C>T	splice_region intron	N/A	ENSP00000499044.1	P42677
RPS27	ENST00000936806.1		c.130-8C>T	splice_region intron	N/A	ENSP00000606865.1
RPS27	ENST00000936804.1		c.128-8C>T	splice_region intron	N/A	ENSP00000606863.1

Frequencies

GnomAD3 genomes

AF:

0.00198

AC:

301

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00702

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.00144

GnomAD2 exomes

AF:

0.000496

AC:

AN:

195728

AF XY:

0.000349

show subpopulations

Gnomad AFR exome

AF:

0.00676

Gnomad AMR exome

AF:

0.000419

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000154

AC:

217

AN:

1405798

Hom.:

Cov.:

AF XY:

0.000126

AC XY:

AN XY:

696696

show subpopulations

African (AFR)

AF:

0.00559

AC:

175

AN:

31294

American (AMR)

AF:

0.000361

AC:

AN:

36034

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24238

East Asian (EAS)

AF:

0.00

AC:

AN:

38606

South Asian (SAS)

AF:

0.0000244

AC:

AN:

81838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51042

Middle Eastern (MID)

AF:

0.000247

AC:

AN:

4046

European-Non Finnish (NFE)

AF:

0.00000370

AC:

AN:

1080946

Other (OTH)

AF:

0.000381

AC:

AN:

57754

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00198

AC:

301

AN:

152246

Hom.:

Cov.:

AF XY:

0.00204

AC XY:

152

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.00700

AC:

291

AN:

41556

American (AMR)

AF:

0.000392

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68004

Other (OTH)

AF:

0.00142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.000935

Hom.:

Bravo

AF:

0.00219

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

RPS27-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

7.3

(source)

DANN

Benign

0.87

PhyloP100

1.1

PromoterAI

-0.042

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000083

dbscSNV1_RF

Benign

0.0

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over