rs213208

Variant names:

• chr6-33210233-G-T
• rs213208
• NM_002931.4:c.455+103G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002931.4(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 NM_002931.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135
• Publications: 20 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Illumina

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RING1	NM_002931.4	c.455+103G>T		intron_variant	Intron 4 of 6	ENST00000374656.5	NP_002922.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RING1	ENST00000374656.5	c.455+103G>T		intron_variant	Intron 4 of 6	1	NM_002931.4	ENSP00000363787.4
RING1	ENST00000478431.1	n.443+103G>T		intron_variant	Intron 2 of 4	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

African (AFR) AF: 0.353 AC: 7518 AN: 21284

American (AMR) AF: 0.203 AC: 6894 AN: 33940

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 3815 AN: 20514

East Asian (EAS) AF: 0.651 AC: 21561 AN: 33144

South Asian (SAS) AF: 0.296 AC: 20042 AN: 67818

European-Finnish (FIN) AF: 0.260 AC: 9387 AN: 36098

Middle Eastern (MID) AF: 0.252 AC: 1069 AN: 4238

European-Non Finnish (NFE) AF: 0.235 AC: 141001 AN: 599706

Other (OTH) AF: 0.264 AC: 10597 AN: 40124

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

African (AFR) AF: 0.364 AC: 15054 AN: 41382

American (AMR) AF: 0.229 AC: 3505 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 582 AN: 3462

East Asian (EAS) AF: 0.639 AC: 3300 AN: 5164

South Asian (SAS) AF: 0.302 AC: 1454 AN: 4816

European-Finnish (FIN) AF: 0.270 AC: 2856 AN: 10568

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.235 AC: 15990 AN: 67978

Other (OTH) AF: 0.304 AC: 640 AN: 2108

Alfa AF: 0.257 Hom.: 6972

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
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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