Genetic Variant RRS1:p.Thr210Thr (chr8-66429761-C-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015169.4(RRS1):c.630C>G(p.Thr210Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00273 in 1,612,680 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 68 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 42 hom. )

Consequence

RRS1
NM_015169.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.11

Variant links:

Genes affected

RRS1 (HGNC:17083): (ribosome biogenesis regulator 1 homolog) Enables 5S rRNA binding activity. Involved in several processes, including mitotic metaphase plate congression; protein localization to nucleolus; and ribosomal large subunit assembly. Located in condensed nuclear chromosome; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RRS1 links:

ENSG00000287127 (HGNC:):

ENSG00000287127 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 8-66429761-C-G is Benign according to our data. Variant chr8-66429761-C-G is described in ClinVar as [Benign]. Clinvar id is 716961.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.11 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRS1	NM_015169.4 link	c.630C>G	p.Thr210Thr	synonymous_variant	Exon 1 of 1	ENST00000320270.4	NP_055984.1	Q15050

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRS1	ENST00000320270.4 link	c.630C>G	p.Thr210Thr	synonymous_variant	Exon 1 of 1	6	NM_015169.4	ENSP00000322396.2		Q15050
ENSG00000287127	ENST00000659008.1 link	n.87+2523G>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.0153

AC:

2321

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0528

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00648

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:

0.000206

Gnomad OTH

AF:

0.00864

GnomAD3 exomes

AF:

0.00359

AC:

875

AN:

243904

Hom.:

AF XY:

0.00267

AC XY:

357

AN XY:

133740

show subpopulations

Gnomad AFR exome

AF:

0.0525

Gnomad AMR exome

AF:

0.00261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000110

Gnomad OTH exome

AF:

0.00184

GnomAD4 exome

AF:

0.00143

AC:

2082

AN:

1460388

Hom.:

Cov.:

AF XY:

0.00123

AC XY:

891

AN XY:

726502

show subpopulations

Gnomad4 AFR exome

AF:

0.0483

Gnomad4 AMR exome

AF:

0.00293

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000881

Gnomad4 OTH exome

AF:

0.00354

GnomAD4 genome

AF:

0.0152

AC:

2322

AN:

152292

Hom.:

Cov.:

AF XY:

0.0147

AC XY:

1098

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0527

Gnomad4 AMR

AF:

0.00647

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00855

Alfa

AF:

0.000608

Hom.:

Bravo

AF:

0.0168

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

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

- -

Jan 12, 2018

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.72

CADD

Benign

1.2

DANN

Benign

0.86

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