rs213208

Positions:

• chr6-33210233-G-T

Variant summary

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

The ENST00000374656.5(RING1):​c.455+103G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,008,834 control chromosomes in the GnomAD database, including 39,374 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 0.29 (6981 hom., cov: 31)
  • Exomes 𝑓: 0.26 (32393 hom.)
• Consequence: RING1 ENST00000374656.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RING1	NM_002931.4	c.455+103G>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.455+103G>T		intron_variant		1	NM_002931.4	ENSP00000363787	P1
RING1	ENST00000478431.1	n.443+103G>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43502 AN: 151850 Hom.: 6954 Cov.: 31

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.295

GnomAD4 exome AF: 0.259 AC: 221884 AN: 856866 Hom.: 32393 AF XY: 0.260 AC XY: 113732 AN XY: 438056

Gnomad4 AFR exome AF: 0.353

Gnomad4 AMR exome AF: 0.203

Gnomad4 ASJ exome AF: 0.186

Gnomad4 EAS exome AF: 0.651

Gnomad4 SAS exome AF: 0.296

Gnomad4 FIN exome AF: 0.260

Gnomad4 NFE exome AF: 0.235

Gnomad4 OTH exome AF: 0.264

GnomAD4 genome AF: 0.287 AC: 43577 AN: 151968 Hom.: 6981 Cov.: 31 AF XY: 0.289 AC XY: 21442 AN XY: 74300

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.639

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.304

Alfa AF: 0.241 Hom.: 2975

Bravo AF: 0.292

Asia WGS AF: 0.388 AC: 1344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.56

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: rs213208; hg19: chr6-33178010; COSMIC: COSV63002261; COSMIC: COSV63002261;