3-72388262-C-T

Variant names:

• chr3-72388262-C-T
• rs9863706
• NM_012234.7:c.129-8835G>A

Variant summary

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

The NM_012234.7(RYBP):​c.129-8835G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 151,974 control chromosomes in the GnomAD database, including 3,720 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 0.22 (3720 hom., cov: 32)
• Consequence: RYBP NM_012234.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260
• Publications: 40 publications found

Genes affected

RYBP (HGNC:10480): (RING1 and YY1 binding protein) Predicted to enable DNA binding activity and transcription coregulator activity. Involved in several processes, including histone H2A monoubiquitination; negative regulation of proteasomal ubiquitin-dependent protein catabolic process; and positive regulation of transcription, DNA-templated. Located in nucleoplasm. Colocalizes with PcG protein complex. [provided by Alliance of Genome Resources, Apr 2022]

RYBP Gene-Disease associations (from GenCC):

• complex 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012234.7. 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
	RYBP	NM_012234.7	MANE Select	c.129-8835G>A		intron	N/A	NP_036366.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RYBP	ENST00000477973.5	TSL:1	c.126-8835G>A		intron	N/A	ENSP00000419494.4	Q8N488

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33334 AN: 151856 Hom.: 3717 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.219 AC: 33348 AN: 151974 Hom.: 3720 Cov.: 32 AF XY: 0.220 AC XY: 16321 AN XY: 74298

African (AFR) AF: 0.232 AC: 9590 AN: 41400

American (AMR) AF: 0.240 AC: 3660 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 546 AN: 3466

East Asian (EAS) AF: 0.252 AC: 1302 AN: 5174

South Asian (SAS) AF: 0.176 AC: 848 AN: 4828

European-Finnish (FIN) AF: 0.175 AC: 1851 AN: 10570

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14868 AN: 67958

Other (OTH) AF: 0.225 AC: 474 AN: 2106

Alfa AF: 0.215 Hom.: 14050

Bravo AF: 0.223

Asia WGS AF: 0.186 AC: 646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.4
DANN	Benign	0.56
PhyloP100		0.026

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: rs9863706; hg19: chr3-72437413;