X-16845886-T-C

Position:

chrX-16845886-T-C

Variant summary

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

The NM_002893.4(RBBP7):c.1151A>G(p.Asn384Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000859 in 1,210,049 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 27 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: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000093 ( 0 hom. 27 hem. )

Consequence

RBBP7
NM_002893.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.14

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=0.19741654).

BS2

High Hemizygotes in GnomAdExome4 at 27 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBBP7	NM_002893.4 linkuse as main transcript	c.1151A>G	p.Asn384Ser	missense_variant	11/12	ENST00000380087.7	NP_002884.1	Q16576-1Q6FHQ0
RBBP7	NM_001198719.2 linkuse as main transcript	c.1283A>G	p.Asn428Ser	missense_variant	11/12		NP_001185648.1	Q16576-2
RBBP7	XM_047442291.1 linkuse as main transcript	c.1418A>G	p.Asn473Ser	missense_variant	11/12		XP_047298247.1
RBBP7	XM_047442292.1 linkuse as main transcript	c.1286A>G	p.Asn429Ser	missense_variant	11/12		XP_047298248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBBP7	ENST00000380087.7 linkuse as main transcript	c.1151A>G	p.Asn384Ser	missense_variant	11/12	1	NM_002893.4	ENSP00000369427.3		Q16576-1

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112154

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34330

show subpopulations

Gnomad AFR

AF:

0.0000325

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000664

GnomAD3 exomes

AF:

0.000137

AC:

AN:

182398

Hom.:

AF XY:

0.000120

AC XY:

AN XY:

66912

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000515

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000531

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000110

Gnomad OTH exome

AF:

0.000222

GnomAD4 exome

AF:

0.0000929

AC:

102

AN:

1097895

Hom.:

Cov.:

AF XY:

0.0000743

AC XY:

AN XY:

363277

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000427

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.0000740

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000926

Gnomad4 OTH exome

AF:

0.0000868

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112154

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34330

show subpopulations

Gnomad4 AFR

AF:

0.0000325

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000664

Bravo

AF:

0.0000718

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

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 22, 2024

The c.1283A>G (p.N428S) alteration is located in exon 11 (coding exon 11) of the RBBP7 gene. This alteration results from a A to G substitution at nucleotide position 1283, causing the asparagine (N) at amino acid position 428 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

0.069

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.062

T;T;.;.

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.87

D;D;D;D

M_CAP

Benign

0.038

MetaRNN

Benign

0.20

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.99

.;L;.;.

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.3

D;D;D;D

REVEL

Benign

0.067

Sift

Benign

0.12

T;T;T;T

Sift4G

Benign

0.27

T;T;T;T

Polyphen

0.034, 0.014

.;B;.;B

Vest4

0.38, 0.44, 0.42

MutPred

0.41

.;Gain of loop (P = 0.1069);.;.;

MVP

0.87

MPC

1.1

ClinPred

0.065

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.37

gMVP

0.41

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