3-72388262-C-T

Position:

• chr3-72388262-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYBP	NM_012234.7	c.129-8835G>A		intron_variant			NP_036366.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYBP	ENST00000477973.5	c.126-8835G>A		intron_variant		1		ENSP00000419494.4

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

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.225

Alfa AF: 0.210 Hom.: 6282

Bravo AF: 0.223

Asia WGS AF: 0.186 AC: 646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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: rs9863706; hg19: chr3-72437413;