6-33210005-C-T

Position:

• chr6-33210005-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.716

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]

ACMG classification

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	UniProt
RING1	NM_002931.4	c.330C>T	p.Ile110=	synonymous_variant	4/7	ENST00000374656.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RING1	ENST00000374656.5	c.330C>T	p.Ile110=	synonymous_variant	4/7	1	NM_002931.4	P1
RING1	ENST00000478431.1	n.318C>T		non_coding_transcript_exon_variant	2/5	1

Frequencies

GnomAD3 genomes AF: 0.00932 AC: 1419 AN: 152212 Hom.: 11 Cov.: 32

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.: 18 AF XY: 0.00906 AC XY: 1232 AN XY: 135916

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.: 32 AF XY: 0.0114 AC XY: 8272 AN XY: 727244

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.: 11 Cov.: 32 AF XY: 0.00920 AC XY: 685 AN XY: 74488

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.: 9

Bravo AF: 0.00962

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0172

EpiControl AF: 0.0155

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	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	14
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

Other links and lift over

dbSNP: rs61736933; hg19: chr6-33177782; COSMIC: COSV100761851; COSMIC: COSV100761851;