chr6-33209181-C-A

Variant names:

• chr6-33209181-C-A
• rs213209
• NM_002931.4:c.78+281C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002931.4(RING1):​c.78+281C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RING1 NM_002931.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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>A		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>A		intron	N/A	ENSP00000363787.4
	RING1	ENST00000869802.1		c.78+281C>A		intron	N/A	ENSP00000539861.1
	RING1	ENST00000869800.1		c.78+281C>A		intron	N/A	ENSP00000539859.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 512056 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 276472

African (AFR) AF: 0.00 AC: 0 AN: 15020

American (AMR) AF: 0.00 AC: 0 AN: 32404

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18400

East Asian (EAS) AF: 0.00 AC: 0 AN: 30236

South Asian (SAS) AF: 0.00 AC: 0 AN: 59770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29920

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3912

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 293730

Other (OTH) AF: 0.00 AC: 0 AN: 28664

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.0
DANN	Benign	0.62
PhyloP100		-0.38

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;