rs17854844

Variant names:

• chr1-205103941-C-A
• rs17854844
• NM_005057.4:c.438G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-205103941-C-A
• chr1-205103941-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_005057.4(RBBP5):​c.438G>T​(p.Pro146Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P146P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBBP5 NM_005057.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.99
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP7: Synonymous conserved (PhyloP=-2.99 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBBP5	NM_005057.4	MANE Select	c.438G>T	p.Pro146Pro	synonymous	Exon 5 of 14	NP_005048.2
	RBBP5	NM_001193272.2		c.438G>T	p.Pro146Pro	synonymous	Exon 5 of 14	NP_001180201.1	Q15291-2
	RBBP5	NM_001193273.2		c.57G>T	p.Pro19Pro	synonymous	Exon 5 of 14	NP_001180202.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBBP5	ENST00000264515.11	TSL:1 MANE Select	c.438G>T	p.Pro146Pro	synonymous	Exon 5 of 14	ENSP00000264515.6	Q15291-1
	RBBP5	ENST00000367164.1	TSL:1	c.438G>T	p.Pro146Pro	synonymous	Exon 5 of 14	ENSP00000356132.1	Q15291-2
	RBBP5	ENST00000861178.1		c.438G>T	p.Pro146Pro	synonymous	Exon 5 of 14	ENSP00000531237.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	4.7
DANN	Benign	0.69
PhyloP100		-3.0
Mutation Taster		=99/1	polymorphism

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: rs17854844; hg19: chr1-205073069;