11-6600781-G-A

Variant names:

• chr11-6600781-G-A
• rs115960367
• NM_015324.4:c.1048-6C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_015324.4(RRP8):​c.1048-6C>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 0.000816 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, intron
• Scores: Splicing: ADA: 0.00004244
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.547
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RRP8	NM_015324.4	c.1048-6C>T		splice_region_variant, intron_variant	Intron 4 of 6	ENST00000254605.11	NP_056139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRP8	ENST00000254605.11	c.1048-6C>T		splice_region_variant, intron_variant	Intron 4 of 6	1	NM_015324.4	ENSP00000254605.6
RRP8	ENST00000534343.1	c.100-6C>T		splice_region_variant, intron_variant	Intron 1 of 3	2		ENSP00000436960.1
RRP8	ENST00000526352.5	n.380-6C>T		splice_region_variant, intron_variant	Intron 1 of 2	2
RRP8	ENST00000533907.1	n.*220-6C>T		splice_region_variant, intron_variant	Intron 3 of 4	5		ENSP00000436246.1

Frequencies

GnomAD3 genomes AF: 0.00411 AC: 625 AN: 152190 Hom.: 7 Cov.: 32

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

GnomAD2 exomes AF: 0.00118 AC: 296 AN: 251330 AF XY: 0.000869

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 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.: 6 Cov.: 31 AF XY: 0.000436 AC XY: 317 AN XY: 726820

African (AFR) AF: 0.0154 AC: 514 AN: 33466

American (AMR) AF: 0.000894 AC: 40 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00106 AC: 6 AN: 5660

European-Non Finnish (NFE) AF: 0.0000378 AC: 42 AN: 1111188

Other (OTH) AF: 0.00124 AC: 75 AN: 60354

GnomAD4 genome AF: 0.00412 AC: 627 AN: 152308 Hom.: 8 Cov.: 32 AF XY: 0.00404 AC XY: 301 AN XY: 74474

African (AFR) AF: 0.0144 AC: 597 AN: 41578

American (AMR) AF: 0.000915 AC: 14 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68010

Other (OTH) AF: 0.00427 AC: 9 AN: 2108

Alfa AF: 0.00214 Hom.: 2

Bravo AF: 0.00476

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 08, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.2
DANN	Benign	0.62
PhyloP100		0.55
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs115960367; hg19: chr11-6622011;