X-16869637-G-A

Position:

• chrX-16869637-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002893.4(RBBP7):​c.16+401C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000482 in 1,037,598 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000048 (0 hom. 1 hem.)
• Consequence: RBBP7 NM_002893.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBBP7	NM_002893.4	c.16+401C>T		intron_variant		ENST00000380087.7
RBBP7	NM_001198719.2	c.5C>T	p.Ala2Val	missense_variant	1/12
RBBP7	XM_047442291.1	c.5C>T	p.Ala2Val	missense_variant	1/12
RBBP7	XM_047442292.1	c.16+401C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBBP7	ENST00000380087.7	c.16+401C>T		intron_variant		1	NM_002893.4	P1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000482 AC: 5 AN: 1037598 Hom.: 0 Cov.: 32 AF XY: 0.00000303 AC XY: 1 AN XY: 329890

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000212

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000493

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Uncertain	1.0
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.49	T
M_CAP	Pathogenic	0.77	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.71	T
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Vest4		0.45
MutPred		0.27		Gain of stability (P = 0.0144);
MVP		0.91
MPC		1.3
ClinPred		0.78	D
GERP RS		2.8
gMVP		0.15

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

Other links and lift over

dbSNP: rs1443261041; hg19: chrX-16887760;