rs12956

Positions:

• chr3-72375320-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_012234.6(RYBP):​c.*3065T>C variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.221 in 232,850 control chromosomes in the GnomAD database, including 5,826 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 (3819 hom., cov: 33)
  • Exomes 𝑓: 0.22 (2007 hom.)
• Consequence: RYBP NM_012234.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.58

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYBP	NM_012234.6	c.*3065T>C		3_prime_UTR_variant	4/4		NP_036366.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYBP	ENST00000477973.5	c.*3065T>C		3_prime_UTR_variant	4/4	1		ENSP00000419494	P1
RYBP	ENST00000676660.1	n.4797T>C		non_coding_transcript_exon_variant	3/3
RYBP	ENST00000677329.1	n.3722T>C		non_coding_transcript_exon_variant	4/4

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33806 AN: 152096 Hom.: 3816 Cov.: 33

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.219 AC: 17627 AN: 80636 Hom.: 2007 Cov.: 0 AF XY: 0.216 AC XY: 8007 AN XY: 37126

Gnomad4 AFR exome AF: 0.220

Gnomad4 AMR exome AF: 0.236

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.226

Gnomad4 SAS exome AF: 0.211

Gnomad4 FIN exome AF: 0.194

Gnomad4 NFE exome AF: 0.221

Gnomad4 OTH exome AF: 0.230

GnomAD4 genome AF: 0.222 AC: 33820 AN: 152214 Hom.: 3819 Cov.: 33 AF XY: 0.223 AC XY: 16579 AN XY: 74412

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.226

Alfa AF: 0.225 Hom.: 942

Bravo AF: 0.225

Asia WGS AF: 0.218 AC: 757 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Benign	0.88

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: rs12956; hg19: chr3-72424471;