6-33209181-C-T

Variant names:

• chr6-33209181-C-T
• rs213209
• NM_002931.4:c.78+281C>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.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
• Publications: 13 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002931.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RING1	NM_002931.4	MANE Select	c.78+281C>T		intron	N/A	NP_002922.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RING1	ENST00000374656.5	TSL:1 MANE Select	c.78+281C>T		intron	N/A	ENSP00000363787.4
	RING1	ENST00000869802.1		c.78+281C>T		intron	N/A	ENSP00000539861.1
	RING1	ENST00000869800.1		c.78+281C>T		intron	N/A	ENSP00000539859.1

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

GnomAD2 exomes AF: 0.324 AC: 38107 AN: 117762 AF XY: 0.327

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 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

African (AFR) AF: 0.398 AC: 5964 AN: 15000

American (AMR) AF: 0.226 AC: 7305 AN: 32372

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 5760 AN: 18372

East Asian (EAS) AF: 0.657 AC: 19826 AN: 30198

South Asian (SAS) AF: 0.349 AC: 20827 AN: 59738

European-Finnish (FIN) AF: 0.284 AC: 8478 AN: 29862

Middle Eastern (MID) AF: 0.334 AC: 1302 AN: 3904

European-Non Finnish (NFE) AF: 0.274 AC: 80499 AN: 293396

Other (OTH) AF: 0.312 AC: 8928 AN: 28632

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

African (AFR) AF: 0.398 AC: 16495 AN: 41428

American (AMR) AF: 0.261 AC: 3992 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1063 AN: 3468

East Asian (EAS) AF: 0.646 AC: 3340 AN: 5172

South Asian (SAS) AF: 0.353 AC: 1702 AN: 4820

European-Finnish (FIN) AF: 0.293 AC: 3096 AN: 10556

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18561 AN: 67994

Other (OTH) AF: 0.348 AC: 735 AN: 2112

Alfa AF: 0.300 Hom.: 15941

Bravo AF: 0.328

Asia WGS AF: 0.421 AC: 1461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.7
DANN	Benign	0.53
PhyloP100		-0.38
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: rs213209; hg19: chr6-33176958; COSMIC: COSV63002383; COSMIC: COSV63002383;