NM_005057.4:c.219-3951A>G

Variant names:

• chr1-205109119-T-C
• rs4950982
• NM_005057.4:c.219-3951A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005057.4(RBBP5):​c.219-3951A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,054 control chromosomes in the GnomAD database, including 50,586 homozygotes. 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 0.81 (50586 hom., cov: 31)
• Consequence: RBBP5 NM_005057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 6 publications found

Genes affected

RBBP5 (HGNC:9888): (RB binding protein 5, histone lysine methyltransferase complex subunit) This gene encodes a ubiquitously expressed nuclear protein which belongs to a highly conserved subfamily of WD-repeat proteins. The encoded protein binds directly to retinoblastoma protein, which regulates cell proliferation. It interacts preferentially with the underphosphorylated retinoblastoma protein via the E1A-binding pocket B. Three alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, Jul 2010]

RBBP5 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005057.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBBP5	NM_005057.4	MANE Select	c.219-3951A>G		intron	N/A	NP_005048.2
	RBBP5	NM_001193272.2		c.219-3951A>G		intron	N/A	NP_001180201.1
	RBBP5	NM_001193273.2		c.-163-3951A>G		intron	N/A	NP_001180202.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBBP5	ENST00000264515.11	TSL:1 MANE Select	c.219-3951A>G		intron	N/A	ENSP00000264515.6
	RBBP5	ENST00000367164.1	TSL:1	c.219-3951A>G		intron	N/A	ENSP00000356132.1
	RBBP5	ENST00000484379.1	TSL:2	n.286-3951A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122490 AN: 151936 Hom.: 50570 Cov.: 31

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.929

Gnomad AMR AF: 0.882

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.970

Gnomad SAS AF: 0.912

Gnomad FIN AF: 0.916

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.870

Gnomad OTH AF: 0.845

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.806 AC: 122545 AN: 152054 Hom.: 50586 Cov.: 31 AF XY: 0.810 AC XY: 60228 AN XY: 74322

African (AFR) AF: 0.602 AC: 24907 AN: 41404

American (AMR) AF: 0.882 AC: 13465 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 3019 AN: 3470

East Asian (EAS) AF: 0.970 AC: 5024 AN: 5180

South Asian (SAS) AF: 0.912 AC: 4411 AN: 4834

European-Finnish (FIN) AF: 0.916 AC: 9693 AN: 10586

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.870 AC: 59139 AN: 68002

Other (OTH) AF: 0.847 AC: 1785 AN: 2108

Alfa AF: 0.856 Hom.: 24409

Bravo AF: 0.797

Asia WGS AF: 0.930 AC: 3231 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.45
DANN	Benign	0.41
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4950982; hg19: chr1-205078247;