1-205109119-T-C

Position:

• chr1-205109119-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBBP5	NM_005057.4	c.219-3951A>G		intron_variant		ENST00000264515.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBBP5	ENST00000264515.11	c.219-3951A>G		intron_variant		1	NM_005057.4	P3
RBBP5	ENST00000367164.1	c.219-3951A>G		intron_variant		1		A1
RBBP5	ENST00000484379.1	n.286-3951A>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.602

Gnomad4 AMR AF: 0.882

Gnomad4 ASJ AF: 0.870

Gnomad4 EAS AF: 0.970

Gnomad4 SAS AF: 0.912

Gnomad4 FIN AF: 0.916

Gnomad4 NFE AF: 0.870

Gnomad4 OTH AF: 0.847

Alfa AF: 0.856 Hom.: 21560

Bravo AF: 0.797

Asia WGS AF: 0.930 AC: 3231 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.45
DANN	Benign	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

Other links and lift over

dbSNP: rs4950982; hg19: chr1-205078247;