Variant 11-6600781-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_015324.4(RRP8):c.1048-6C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000816 in 1,613,152 control chromosomes in the GnomAD database, including 14 homozygotes. 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 0.0041 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00047 ( 6 hom. )

Consequence

RRP8
NM_015324.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00004244

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.547

Variant links:

Genes affected

RRP8 (HGNC:29030): (ribosomal RNA processing 8) Enables methylated histone binding activity. Involved in several processes, including cellular response to glucose starvation; intrinsic apoptotic signaling pathway by p53 class mediator; and regulation of gene expression. Located in several cellular components, including cytosol; nuclear lumen; and rDNA heterochromatin. Part of chromatin silencing complex. [provided by Alliance of Genome Resources, Apr 2022]

RRP8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

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

BP6

Variant 11-6600781-G-A is Benign according to our data. Variant chr11-6600781-G-A is described in ClinVar as [Benign]. Clinvar id is 713408.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRP8	NM_015324.4 linkuse as main transcript	c.1048-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000254605.11	NP_056139.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
RRP8	ENST00000254605.11 linkuse as main transcript	c.1048-6C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_015324.4	ENSP00000254605	P1
RRP8	ENST00000534343.1 linkuse as main transcript	c.100-6C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	2		ENSP00000436960
RRP8	ENST00000533907.1 linkuse as main transcript	c.*220-6C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant	5		ENSP00000436246
RRP8	ENST00000526352.5 linkuse as main transcript	n.380-6C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00411

AC:

625

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0143

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00118

AC:

296

AN:

251330

Hom.:

AF XY:

0.000869

AC XY:

118

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.0154

Gnomad AMR exome

AF:

0.000810

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000880

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000472

AC:

689

AN:

1460844

Hom.:

Cov.:

AF XY:

0.000436

AC XY:

317

AN XY:

726820

show subpopulations

Gnomad4 AFR exome

AF:

0.0154

Gnomad4 AMR exome

AF:

0.000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000378

Gnomad4 OTH exome

AF:

0.00124

GnomAD4 genome

AF:

0.00412

AC:

627

AN:

152308

Hom.:

Cov.:

AF XY:

0.00404

AC XY:

301

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0144

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00222

Hom.:

Bravo

AF:

0.00476

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.2

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000042

dbscSNV1_RF

Benign

0.014

SpliceAI score (max)

0.020

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