4-1058283-AGAACGCAGTGAAGAAGGTGCTTGCGGGGG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001366919.1(RNF212):c.647+9_647+37del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0461 in 144,794 control chromosomes in the GnomAD database, including 253 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.046 (253 hom., cov: 27)
  • Exomes 𝑓: 0.047 (3059 hom.)
  • Failed GnomAD Quality Control
• Consequence: RNF212 NM_001366919.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.598

Genes affected

RNF212 (HGNC:27729): (ring finger protein 212) This gene encodes a RING finger protein that may function as a ubiquitin ligase. The encoded protein may be involved in meiotic recombination. This gene is located within a linkage disequilibrium block and polymorphisms in this gene may influence recombination rates. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 4-1058283-AGAACGCAGTGAAGAAGGTGCTTGCGGGGG-A is Benign according to our data. Variant chr4-1058283-AGAACGCAGTGAAGAAGGTGCTTGCGGGGG-A is described in ClinVar as [Likely_benign]. Clinvar id is 3033074.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF212	NM_001366918.1	c.647+9_647+37del		intron_variant
RNF212	NM_001366919.1	c.647+9_647+37del		intron_variant
RNF212	XM_011513446.2	c.383+9_383+37del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF212	ENST00000698262.1	c.647+9_647+37del		intron_variant				P2
RNF212	ENST00000506730.5	c.*426+9_*426+37del		intron_variant, NMD_transcript_variant		3
RNF212	ENST00000503206.5	n.220+9_220+37del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0461 AC: 6672 AN: 144702 Hom.: 253 Cov.: 27

Gnomad AFR AF: 0.0392

Gnomad AMI AF: 0.0133

Gnomad AMR AF: 0.0443

Gnomad ASJ AF: 0.0548

Gnomad EAS AF: 0.00315

Gnomad SAS AF: 0.0116

Gnomad FIN AF: 0.0276

Gnomad MID AF: 0.0888

Gnomad NFE AF: 0.0581

Gnomad OTH AF: 0.0628

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0471 AC: 27149 AN: 576688 Hom.: 3059 AF XY: 0.0468 AC XY: 12580 AN XY: 268740

Gnomad4 AFR exome AF: 0.0285

Gnomad4 AMR exome AF: 0.0323

Gnomad4 ASJ exome AF: 0.0383

Gnomad4 EAS exome AF: 0.0180

Gnomad4 SAS exome AF: 0.0222

Gnomad4 FIN exome AF: 0.0403

Gnomad4 NFE exome AF: 0.0484

Gnomad4 OTH exome AF: 0.0405

GnomAD4 genome AF: 0.0461 AC: 6671 AN: 144794 Hom.: 253 Cov.: 27 AF XY: 0.0431 AC XY: 3049 AN XY: 70684

Gnomad4 AFR AF: 0.0391

Gnomad4 AMR AF: 0.0443

Gnomad4 ASJ AF: 0.0548

Gnomad4 EAS AF: 0.00315

Gnomad4 SAS AF: 0.0122

Gnomad4 FIN AF: 0.0276

Gnomad4 NFE AF: 0.0581

Gnomad4 OTH AF: 0.0623

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

RNF212-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 09, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1392105979; hg19: chr4-1052071;