Variant chr6-33211285-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002931.4(RING1):c.583G>A(p.Ala195Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000683 in 1,611,236 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00065 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00069 ( 4 hom. )

Consequence

RING1
NM_002931.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.633

Variant links:

Genes affected

RING1 (HGNC:10018): (ring finger protein 1) This gene belongs to the RING finger family, members of which encode proteins characterized by a RING domain, a zinc-binding motif related to the zinc finger domain. The gene product can bind DNA and can act as a transcriptional repressor. It is associated with the multimeric polycomb group protein complex. The gene product interacts with the polycomb group proteins BMI1, EDR1, and CBX4, and colocalizes with these proteins in large nuclear domains. It interacts with the CBX4 protein via its glycine-rich C-terminal domain. The gene maps to the HLA class II region, where it is contiguous with the RING finger genes FABGL and HKE4. [provided by RefSeq, Jul 2008]

RING1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042042136).

BP6

Variant 6-33211285-G-A is Benign according to our data. Variant chr6-33211285-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2229718.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 98 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RING1	NM_002931.4 linkuse as main transcript	c.583G>A	p.Ala195Thr	missense_variant	5/7	ENST00000374656.5	NP_002922.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RING1	ENST00000374656.5 linkuse as main transcript	c.583G>A	p.Ala195Thr	missense_variant	5/7	1	NM_002931.4	ENSP00000363787	P1	Q06587-1
RING1	ENST00000478431.1 linkuse as main transcript	n.571G>A		non_coding_transcript_exon_variant	3/5	1

Frequencies

GnomAD3 genomes

AF:

0.000660

AC:

100

AN:

151438

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00807

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00125

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000545

Gnomad OTH

AF:

0.000960

GnomAD3 exomes

AF:

0.000919

AC:

225

AN:

244950

Hom.:

AF XY:

0.00101

AC XY:

135

AN XY:

133784

show subpopulations

Gnomad AFR exome

AF:

0.000134

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.00737

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.000922

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000667

Gnomad OTH exome

AF:

0.000991

GnomAD4 exome

AF:

0.000687

AC:

1003

AN:

1459698

Hom.:

Cov.:

AF XY:

0.000737

AC XY:

535

AN XY:

726156

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.00896

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000615

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000473

Gnomad4 OTH exome

AF:

0.00118

GnomAD4 genome

AF:

0.000647

AC:

AN:

151538

Hom.:

Cov.:

AF XY:

0.000688

AC XY:

AN XY:

74078

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.00151

Gnomad4 ASJ

AF:

0.00807

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000545

Gnomad4 OTH

AF:

0.000950

Alfa

AF:

0.00113

Hom.:

Bravo

AF:

0.000759

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000331

AC:

ESP6500EA

AF:

0.000555

AC:

ExAC

AF:

0.000861

AC:

101

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00109

EpiControl

AF:

0.00119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 28, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.041

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.57

M_CAP

Benign

0.013

MetaRNN

Benign

0.0042

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.94

PrimateAI

Uncertain

0.73

PROVEAN

Benign

0.73

REVEL

Benign

0.072

Sift

Benign

0.61

Sift4G

Benign

0.78

Polyphen

0.0

Vest4

0.16

MVP

0.38

MPC

0.55

ClinPred

0.0047

GERP RS

1.3

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.043

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over