rs213209

Positions:

• chr6-33209181-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002931.4(RING1):​c.78+281C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 663,508 control chromosomes in the GnomAD database, including 35,909 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 0.32 (8630 hom., cov: 32)
  • Exomes 𝑓: 0.31 (27279 hom.)
• Consequence: RING1 NM_002931.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RING1	NM_002931.4	c.78+281C>T		intron_variant		ENST00000374656.5	NP_002922.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RING1	ENST00000374656.5	c.78+281C>T		intron_variant		1	NM_002931.4	ENSP00000363787	P1

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49133 AN: 151916 Hom.: 8602 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.341

GnomAD3 exomes AF: 0.324 AC: 38107 AN: 117762 Hom.: 6956 AF XY: 0.327 AC XY: 20981 AN XY: 64230

Gnomad AFR exome AF: 0.394

Gnomad AMR exome AF: 0.218

Gnomad ASJ exome AF: 0.322

Gnomad EAS exome AF: 0.650

Gnomad SAS exome AF: 0.359

Gnomad FIN exome AF: 0.289

Gnomad NFE exome AF: 0.279

Gnomad OTH exome AF: 0.318

GnomAD4 exome AF: 0.311 AC: 158889 AN: 511474 Hom.: 27279 Cov.: 0 AF XY: 0.313 AC XY: 86420 AN XY: 276196

Gnomad4 AFR exome AF: 0.398

Gnomad4 AMR exome AF: 0.226

Gnomad4 ASJ exome AF: 0.314

Gnomad4 EAS exome AF: 0.657

Gnomad4 SAS exome AF: 0.349

Gnomad4 FIN exome AF: 0.284

Gnomad4 NFE exome AF: 0.274

Gnomad4 OTH exome AF: 0.312

GnomAD4 genome AF: 0.324 AC: 49206 AN: 152034 Hom.: 8630 Cov.: 32 AF XY: 0.325 AC XY: 24133 AN XY: 74316

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.348

Alfa AF: 0.293 Hom.: 9190

Bravo AF: 0.328

Asia WGS AF: 0.421 AC: 1461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.7
DANN	Benign	0.53

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: rs213209; hg19: chr6-33176958; COSMIC: COSV63002383; COSMIC: COSV63002383;