4-1058312-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001366919.1(RNF212):c.647+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0331 in 125,840 control chromosomes in the GnomAD database, including 346 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (346 hom., cov: 29)
  • Exomes 𝑓: 0.011 (1510 hom.)
  • Failed GnomAD Quality Control
• Consequence: RNF212 NM_001366919.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.35

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 4-1058312-G-A is Benign according to our data. Variant chr4-1058312-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3032404.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF212	NM_001366918.1	c.647+9C>T		intron_variant
RNF212	NM_001366919.1	c.647+9C>T		intron_variant
RNF212	XM_011513446.2	c.383+9C>T		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0331 AC: 4158 AN: 125744 Hom.: 347 Cov.: 29

Gnomad AFR AF: 0.0738

Gnomad AMI AF: 0.0161

Gnomad AMR AF: 0.0243

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.0168

Gnomad SAS AF: 0.0197

Gnomad FIN AF: 0.0188

Gnomad MID AF: 0.00855

Gnomad NFE AF: 0.0147

Gnomad OTH AF: 0.0301

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0108 AC: 6380 AN: 592384 Hom.: 1510 Cov.: 0 AF XY: 0.0113 AC XY: 3083 AN XY: 273722

Gnomad4 AFR exome AF: 0.0120

Gnomad4 AMR exome AF: 0.00928

Gnomad4 ASJ exome AF: 0.0109

Gnomad4 EAS exome AF: 0.00882

Gnomad4 SAS exome AF: 0.0100

Gnomad4 FIN exome AF: 0.0121

Gnomad4 NFE exome AF: 0.0106

Gnomad4 OTH exome AF: 0.0121

GnomAD4 genome AF: 0.0331 AC: 4163 AN: 125840 Hom.: 346 Cov.: 29 AF XY: 0.0328 AC XY: 2025 AN XY: 61692

Gnomad4 AFR AF: 0.0738

Gnomad4 AMR AF: 0.0242

Gnomad4 ASJ AF: 0.0190

Gnomad4 EAS AF: 0.0171

Gnomad4 SAS AF: 0.0188

Gnomad4 FIN AF: 0.0188

Gnomad4 NFE AF: 0.0147

Gnomad4 OTH AF: 0.0304

Alfa AF: 0.153 Hom.: 308

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

Mar 11, 2022

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	6.0
Dann	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs57186616; hg19: chr4-1052100;