Variant 6-33210005-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_002931.4(RING1):c.330C>T(p.Ile110=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,614,216 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0093 ( 11 hom., cov: 32)

Exomes 𝑓: 0.011 ( 120 hom. )

Consequence

RING1
NM_002931.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.716

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 6-33210005-C-T is Benign according to our data. Variant chr6-33210005-C-T is described in ClinVar as [Benign]. Clinvar id is 791566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.716 with no splicing effect.

BS2

High AC in GnomAd4 at 1420 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RING1	NM_002931.4 linkuse as main transcript	c.330C>T	p.Ile110=	synonymous_variant	4/7	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.330C>T	p.Ile110=	synonymous_variant	4/7	1	NM_002931.4	ENSP00000363787	P1	Q06587-1
RING1	ENST00000478431.1 linkuse as main transcript	n.318C>T		non_coding_transcript_exon_variant	2/5	1

Frequencies

GnomAD3 genomes

AF:

0.00932

AC:

1419

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00316

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0128

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0150

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00863

AC:

2171

AN:

251474

Hom.:

AF XY:

0.00906

AC XY:

1232

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00258

Gnomad AMR exome

AF:

0.00781

Gnomad ASJ exome

AF:

0.00456

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.00343

Gnomad FIN exome

AF:

0.00240

Gnomad NFE exome

AF:

0.0141

Gnomad OTH exome

AF:

0.00798

GnomAD4 exome

AF:

0.0114

AC:

16651

AN:

1461886

Hom.:

120

Cov.:

AF XY:

0.0114

AC XY:

8272

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00152

Gnomad4 AMR exome

AF:

0.00774

Gnomad4 ASJ exome

AF:

0.00375

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.00370

Gnomad4 FIN exome

AF:

0.00300

Gnomad4 NFE exome

AF:

0.0135

Gnomad4 OTH exome

AF:

0.00972

GnomAD4 genome

AF:

0.00932

AC:

1420

AN:

152330

Hom.:

Cov.:

AF XY:

0.00920

AC XY:

685

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00315

Gnomad4 AMR

AF:

0.0128

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.0150

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0118

Hom.:

Bravo

AF:

0.00962

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0172

EpiControl

AF:

0.0155

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	RING1: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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