dbSNP rs12956: RYBP:c.*3065T>C (chr3-72375320-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_012234.7(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_012234.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.58

Publications

10 publications found

Variant links:

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

RYBP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RYBP	NM_012234.7 link	c.*3065T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000643872.4	NP_036366.3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
RYBP	ENST00000477973.5 link	c.*3065T>C	3_prime_UTR_variant	Exon 4 of 4	1	ENSP00000419494.4
RYBP	ENST00000676660.1 link	n.4797T>C	non_coding_transcript_exon_variant	Exon 3 of 3
RYBP	ENST00000677329.1 link	n.3722T>C	non_coding_transcript_exon_variant	Exon 4 of 4

Frequencies

GnomAD3 genomes

AF:

0.222

AC:

33806

AN:

152096

Hom.:

3816

Cov.:

show subpopulations

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.:

AF XY:

0.216

AC XY:

8007

AN XY:

37126

show subpopulations

African (AFR)

AF:

0.220

AC:

847

AN:

3842

American (AMR)

AF:

0.236

AC:

586

AN:

2482

Ashkenazi Jewish (ASJ)

AF:

0.155

AC:

789

AN:

5096

East Asian (EAS)

AF:

0.226

AC:

2542

AN:

11254

South Asian (SAS)

AF:

0.211

AC:

147

AN:

698

European-Finnish (FIN)

AF:

0.194

AC:

AN:

484

Middle Eastern (MID)

AF:

0.199

AC:

AN:

488

European-Non Finnish (NFE)

AF:

0.221

AC:

10988

AN:

49608

Other (OTH)

AF:

0.230

AC:

1537

AN:

6684

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

702

1405

2107

2810

3512

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.222

AC:

33820

AN:

152214

Hom.:

3819

Cov.:

AF XY:

0.223

AC XY:

16579

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.217

AC:

9032

AN:

41544

American (AMR)

AF:

0.243

AC:

3712

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.160

AC:

555

AN:

3472

East Asian (EAS)

AF:

0.295

AC:

1527

AN:

5178

South Asian (SAS)

AF:

0.187

AC:

905

AN:

4832

European-Finnish (FIN)

AF:

0.192

AC:

2032

AN:

10580

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.226

AC:

15364

AN:

67990

Other (OTH)

AF:

0.226

AC:

479

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1394

2787

4181

5574

6968

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

360

720

1080

1440

1800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.88

PhyloP100

4.6

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over