4-1058378-A-C

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.590T>G(p.Leu197Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 429,284 control chromosomes in the GnomAD database, including 116,838 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.82 (49830 hom., cov: 30)
  • Exomes 𝑓: 0.66 (67008 hom.)
• Consequence: RNF212 NM_001366919.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.17

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=-0.89).
• BP6: Variant 4-1058378-A-C is Benign according to our data. Variant chr4-1058378-A-C is described in ClinVar as [Benign]. Clinvar id is 3047327.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF212	NM_001366919.1	c.590T>G	p.Leu197Arg	missense_variant	10/12
RNF212	NM_001366918.1	c.590T>G	p.Leu197Arg	missense_variant	10/11
RNF212	XM_047450082.1	c.790T>G	p.Trp264Gly	missense_variant	11/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF212	ENST00000698262.1	c.590T>G	p.Leu197Arg	missense_variant	10/12			P2
RNF212	ENST00000503206.5	n.163T>G		non_coding_transcript_exon_variant	4/5	3
RNF212	ENST00000505693.5	n.517T>G		non_coding_transcript_exon_variant	4/6	5

Frequencies

GnomAD3 genomes AF: 0.822 AC: 118597 AN: 144356 Hom.: 49798 Cov.: 30

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.805

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.814

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.806

GnomAD4 exome AF: 0.662 AC: 188548 AN: 284816 Hom.: 67008 Cov.: 0 AF XY: 0.660 AC XY: 87053 AN XY: 131838

Gnomad4 AFR exome AF: 0.913

Gnomad4 AMR exome AF: 0.503

Gnomad4 ASJ exome AF: 0.661

Gnomad4 EAS exome AF: 0.477

Gnomad4 SAS exome AF: 0.621

Gnomad4 FIN exome AF: 0.757

Gnomad4 NFE exome AF: 0.660

Gnomad4 OTH exome AF: 0.648

GnomAD4 genome AF: 0.821 AC: 118676 AN: 144468 Hom.: 49830 Cov.: 30 AF XY: 0.818 AC XY: 57545 AN XY: 70362

Gnomad4 AFR AF: 0.943

Gnomad4 AMR AF: 0.690

Gnomad4 ASJ AF: 0.805

Gnomad4 EAS AF: 0.638

Gnomad4 SAS AF: 0.771

Gnomad4 FIN AF: 0.819

Gnomad4 NFE AF: 0.796

Gnomad4 OTH AF: 0.805

Alfa AF: 0.684 Hom.: 2549

Bravo AF: 0.807

Asia WGS AF: 0.561 AC: 1506 AN: 2680

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

RNF212-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 07, 2022

This variant is classified as 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	-0.89
Cadd	Benign	0.69
Dann	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2248083; hg19: chr4-1052166;