Variant 18-22937066-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_002894.3(RBBP8):c.109+106G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0205 in 1,534,148 control chromosomes in the GnomAD database, including 407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.013 ( 13 hom., cov: 32)

Exomes 𝑓: 0.021 ( 394 hom. )

Consequence

RBBP8
NM_002894.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.365

Variant links:

Genes affected

RBBP8 (HGNC:9891): (RB binding protein 8, endonuclease) The protein encoded by this gene is a ubiquitously expressed nuclear protein. It is found among several proteins that bind directly to retinoblastoma protein, which regulates cell proliferation. This protein complexes with transcriptional co-repressor CTBP. It is also associated with BRCA1 and is thought to modulate the functions of BRCA1 in transcriptional regulation, DNA repair, and/or cell cycle checkpoint control. It is suggested that this gene may itself be a tumor suppressor acting in the same pathway as BRCA1. Three transcript variants encoding two different isoforms have been found for this gene. More transcript variants exist, but their full-length natures have not been determined. [provided by RefSeq, Jul 2008]

RBBP8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 18-22937066-G-C is Benign according to our data. Variant chr18-22937066-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1212649.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0129 (1964/152250) while in subpopulation NFE AF= 0.0225 (1532/68014). AF 95% confidence interval is 0.0216. There are 13 homozygotes in gnomad4. There are 820 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBBP8	NM_002894.3 linkuse as main transcript	c.109+106G>C		intron_variant		ENST00000327155.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBBP8	ENST00000327155.10 linkuse as main transcript	c.109+106G>C		intron_variant		1	NM_002894.3	P1	Q99708-1

Frequencies

GnomAD3 genomes

AF:

0.0129

AC:

1964

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00442

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.00766

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00559

Gnomad FIN

AF:

0.00443

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0225

Gnomad OTH

AF:

0.0144

GnomAD3 exomes

AF:

0.0134

AC:

2038

AN:

151966

Hom.:

AF XY:

0.0135

AC XY:

1114

AN XY:

82352

show subpopulations

Gnomad AFR exome

AF:

0.00385

Gnomad AMR exome

AF:

0.00728

Gnomad ASJ exome

AF:

0.00357

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00918

Gnomad FIN exome

AF:

0.00552

Gnomad NFE exome

AF:

0.0238

Gnomad OTH exome

AF:

0.0131

GnomAD4 exome

AF:

0.0213

AC:

29484

AN:

1381898

Hom.:

394

Cov.:

AF XY:

0.0211

AC XY:

14416

AN XY:

682950

show subpopulations

Gnomad4 AFR exome

AF:

0.00279

Gnomad4 AMR exome

AF:

0.00792

Gnomad4 ASJ exome

AF:

0.00351

Gnomad4 EAS exome

AF:

0.0000282

Gnomad4 SAS exome

AF:

0.00976

Gnomad4 FIN exome

AF:

0.00609

Gnomad4 NFE exome

AF:

0.0251

Gnomad4 OTH exome

AF:

0.0184

GnomAD4 genome

AF:

0.0129

AC:

1964

AN:

152250

Hom.:

Cov.:

AF XY:

0.0110

AC XY:

820

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00441

Gnomad4 AMR

AF:

0.00765

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00560

Gnomad4 FIN

AF:

0.00443

Gnomad4 NFE

AF:

0.0225

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.0135

Hom.:

Bravo

AF:

0.0129

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

DANN

Benign

0.27

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.24

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