1-205103941-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_005057.4(RBBP5):​c.438G>A​(p.Pro146Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00345 in 1,614,084 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0036 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (12 hom.)
• Consequence: RBBP5 NM_005057.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.99
• Publications: 1 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 1-205103941-C-T is Benign according to our data. Variant chr1-205103941-C-T is described in ClinVar as Benign. ClinVar VariationId is 719895.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.99 with no splicing effect.
• BS2: High AC in GnomAd4 at 548 AD gene.

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>A	p.Pro146Pro	synonymous	Exon 5 of 14	NP_005048.2
	RBBP5	NM_001193272.2		c.438G>A	p.Pro146Pro	synonymous	Exon 5 of 14	NP_001180201.1	Q15291-2
	RBBP5	NM_001193273.2		c.57G>A	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>A	p.Pro146Pro	synonymous	Exon 5 of 14	ENSP00000264515.6	Q15291-1
	RBBP5	ENST00000367164.1	TSL:1	c.438G>A	p.Pro146Pro	synonymous	Exon 5 of 14	ENSP00000356132.1	Q15291-2
	RBBP5	ENST00000861178.1		c.438G>A	p.Pro146Pro	synonymous	Exon 5 of 14	ENSP00000531237.1

Frequencies

GnomAD3 genomes AF: 0.00360 AC: 548 AN: 152130 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.000966

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000472

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00373

Gnomad OTH AF: 0.00573

GnomAD2 exomes AF: 0.00266 AC: 668 AN: 251340 AF XY: 0.00251

Gnomad AFR exome AF: 0.000615

Gnomad AMR exome AF: 0.00492

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000508

Gnomad NFE exome AF: 0.00380

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00344 AC: 5027 AN: 1461836 Hom.: 12 Cov.: 30 AF XY: 0.00340 AC XY: 2475 AN XY: 727216

African (AFR) AF: 0.000568 AC: 19 AN: 33478

American (AMR) AF: 0.00534 AC: 239 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000421 AC: 11 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000499 AC: 43 AN: 86258

European-Finnish (FIN) AF: 0.000693 AC: 37 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00403 AC: 4484 AN: 1111962

Other (OTH) AF: 0.00318 AC: 192 AN: 60392

GnomAD4 genome AF: 0.00360 AC: 548 AN: 152248 Hom.: 6 Cov.: 32 AF XY: 0.00364 AC XY: 271 AN XY: 74440

African (AFR) AF: 0.000963 AC: 40 AN: 41526

American (AMR) AF: 0.0137 AC: 209 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.000472 AC: 5 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00373 AC: 254 AN: 68030

Other (OTH) AF: 0.00567 AC: 12 AN: 2116

Alfa AF: 0.00347 Hom.: 2

Bravo AF: 0.00509

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00360

EpiControl AF: 0.00445

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	10
DANN	Benign	0.68
PhyloP100		-3.0
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;