Genetic Variant RPS27:c.115+109C>T (chr1-153991332-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001030.6(RPS27):c.115+109C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0343 in 1,520,826 control chromosomes in the GnomAD database, including 1,087 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 99 hom., cov: 32)

Exomes 𝑓: 0.035 ( 988 hom. )

Consequence

RPS27
NM_001030.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0910

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 1-153991332-C-T is Benign according to our data. Variant chr1-153991332-C-T is described in ClinVar as [Benign]. Clinvar id is 1286485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0287 (4372/152218) while in subpopulation NFE AF= 0.0392 (2668/68010). AF 95% confidence interval is 0.038. There are 99 homozygotes in gnomad4. There are 2250 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 4372 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RPS27	NM_001030.6 link	c.115+109C>T	intron_variant	Intron 2 of 3	ENST00000651669.1	NP_001021.1	P42677
RPS27	NM_001349946.2 link	c.19+109C>T	intron_variant	Intron 3 of 4		NP_001336875.1
RPS27	NM_001349947.2 link	c.19+109C>T	intron_variant	Intron 2 of 3		NP_001336876.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS27	ENST00000651669.1 link	c.115+109C>T		intron_variant	Intron 2 of 3		NM_001030.6	ENSP00000499044.1		P42677

Frequencies

GnomAD3 genomes

AF:

0.0288

AC:

4373

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00608

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0248

Gnomad ASJ

AF:

0.0366

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.0798

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0392

Gnomad OTH

AF:

0.0292

GnomAD3 exomes

AF:

0.0301

AC:

4018

AN:

133320

Hom.:

AF XY:

0.0291

AC XY:

2080

AN XY:

71416

show subpopulations

Gnomad AFR exome

AF:

0.00633

Gnomad AMR exome

AF:

0.0165

Gnomad ASJ exome

AF:

0.0333

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00498

Gnomad FIN exome

AF:

0.0851

Gnomad NFE exome

AF:

0.0357

Gnomad OTH exome

AF:

0.0261

GnomAD4 exome

AF:

0.0349

AC:

47827

AN:

1368608

Hom.:

988

Cov.:

AF XY:

0.0343

AC XY:

23092

AN XY:

673928

show subpopulations

Gnomad4 AFR exome

AF:

0.00540

Gnomad4 AMR exome

AF:

0.0164

Gnomad4 ASJ exome

AF:

0.0374

Gnomad4 EAS exome

AF:

0.0000282

Gnomad4 SAS exome

AF:

0.00568

Gnomad4 FIN exome

AF:

0.0811

Gnomad4 NFE exome

AF:

0.0376

Gnomad4 OTH exome

AF:

0.0321

GnomAD4 genome

AF:

0.0287

AC:

4372

AN:

152218

Hom.:

Cov.:

AF XY:

0.0302

AC XY:

2250

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00606

Gnomad4 AMR

AF:

0.0248

Gnomad4 ASJ

AF:

0.0366

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00497

Gnomad4 FIN

AF:

0.0798

Gnomad4 NFE

AF:

0.0392

Gnomad4 OTH

AF:

0.0289

Alfa

AF:

0.0346

Hom.:

Bravo

AF:

0.0228

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 15, 2021

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

-0.81

CADD

Benign

2.9

DANN

Benign

0.61

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over