Variant X-16852858-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002893.4(RBBP7):c.776A>G(p.Asn259Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000373 in 1,098,114 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.000037 ( 0 hom. 11 hem. )

Consequence

RBBP7
NM_002893.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.01

Variant links:

Genes affected

RBBP7 (HGNC:9890): (RB binding protein 7, chromatin remodeling factor) This protein is a ubiquitously expressed nuclear protein and belongs to a highly conserved subfamily of WD-repeat proteins. It is found among several proteins that binds directly to retinoblastoma protein, which regulates cell proliferation. The encoded protein is found in many histone deacetylase complexes, including mSin3 co-repressor complex. It is also present in protein complexes involved in chromatin assembly. This protein can interact with BRCA1 tumor-suppressor gene and may have a role in the regulation of cell proliferation and differentiation. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

RBBP7 links:

RBBP7 (HGNC:):

RBBP7 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19357511).

BS2

High Hemizygotes in GnomAdExome4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBBP7	NM_002893.4 linkuse as main transcript	c.776A>G	p.Asn259Ser	missense_variant	7/12	ENST00000380087.7	NP_002884.1	Q16576-1Q6FHQ0
RBBP7	NM_001198719.2 linkuse as main transcript	c.908A>G	p.Asn303Ser	missense_variant	7/12		NP_001185648.1	Q16576-2
RBBP7	XM_047442291.1 linkuse as main transcript	c.908A>G	p.Asn303Ser	missense_variant	7/12		XP_047298247.1
RBBP7	XM_047442292.1 linkuse as main transcript	c.776A>G	p.Asn259Ser	missense_variant	7/12		XP_047298248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBBP7	ENST00000380087.7 linkuse as main transcript	c.776A>G	p.Asn259Ser	missense_variant	7/12	1	NM_002893.4	ENSP00000369427.3		Q16576-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000491

AC:

AN:

183192

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67666

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000109

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000612

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.0000373

AC:

AN:

1098114

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

363502

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.0000852

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000369

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000416

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000346

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 19, 2024

The c.908A>G (p.N303S) alteration is located in exon 7 (coding exon 7) of the RBBP7 gene. This alteration results from a A to G substitution at nucleotide position 908, causing the asparagine (N) at amino acid position 303 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.58

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.043

T;.;.;.;.

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.91

D;D;D;D;D

M_CAP

Benign

0.066

MetaRNN

Benign

0.19

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.73

N;.;.;.;.

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.52

N;N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.75

T;T;T;T;T

Sift4G

Benign

0.87

T;T;T;T;.

Polyphen

0.0

B;.;B;.;.

Vest4

0.60

MutPred

0.24

Gain of disorder (P = 0.0478);.;.;.;.;

MVP

0.80

MPC

1.7

ClinPred

0.12

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.37

gMVP

0.44

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