Variant 21-43797542-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_003683.6(RRP1):c.543C>T(p.Gly181Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000989 in 1,613,850 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00094 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00099 ( 13 hom. )

Consequence

RRP1
NM_003683.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.259

Variant links:

Genes affected

RRP1 (HGNC:18785): (ribosomal RNA processing 1) The protein encoded by this gene is the putative homolog of the yeast ribosomal RNA processing protein RRP1. The encoded protein is involved in the late stages of nucleologenesis at the end of mitosis, and may be required for the generation of 28S rRNA. [provided by RefSeq, Jul 2008]

RRP1 links:

RRP1 (HGNC:):

RRP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 21-43797542-C-T is Benign according to our data. Variant chr21-43797542-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 731015.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000994 (1453/1461606) while in subpopulation MID AF= 0.0316 (182/5768). AF 95% confidence interval is 0.0278. There are 13 homozygotes in gnomad4_exome. There are 822 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRP1	NM_003683.6 linkuse as main transcript	c.543C>T	p.Gly181Gly	synonymous_variant	6/13	ENST00000497547.2	NP_003674.1	P56182
RRP1	XM_017028485.3 linkuse as main transcript	c.543C>T	p.Gly181Gly	synonymous_variant	6/13		XP_016883974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRP1	ENST00000497547.2 linkuse as main transcript	c.543C>T	p.Gly181Gly	synonymous_variant	6/13	1	NM_003683.6	ENSP00000417464.1		P56182

Frequencies

GnomAD3 genomes

AF:

0.000940

AC:

143

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.000735

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00106

AC:

263

AN:

248954

Hom.:

AF XY:

0.00121

AC XY:

163

AN XY:

135130

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.000928

Gnomad ASJ exome

AF:

0.000995

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00190

Gnomad FIN exome

AF:

0.0000931

Gnomad NFE exome

AF:

0.00120

Gnomad OTH exome

AF:

0.00348

GnomAD4 exome

AF:

0.000994

AC:

1453

AN:

1461606

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

822

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.00182

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.00115

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00237

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000670

Gnomad4 OTH exome

AF:

0.00283

GnomAD4 genome

AF:

0.000939

AC:

143

AN:

152244

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00262

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000735

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000976

Hom.:

Bravo

AF:

0.000997

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00229

EpiControl

AF:

0.00231

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.75

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.75

Position offset: -6

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