chr4-1056848-C-T

Position:

• chr4-1056848-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001366919.1(RNF212):​c.804G>A​(p.Arg268Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 987,466 control chromosomes in the GnomAD database, including 12,439 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.21 (6469 hom., cov: 33)
  • Exomes 𝑓: 0.099 (5970 hom.)
• Consequence: RNF212 NM_001366919.1 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.144

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]

RNF212 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 4-1056848-C-T is Benign according to our data. Variant chr4-1056848-C-T is described in ClinVar as [Benign]. Clinvar id is 3031982.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.144 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF212	NM_001366919.1	c.804G>A	p.Arg268Arg	synonymous_variant	11/12		NP_001353848.1
RNF212	XM_047450083.1	c.702G>A	p.Arg234Arg	synonymous_variant	9/10		XP_047306039.1
RNF212	XM_011513446.2	c.540G>A	p.Arg180Arg	synonymous_variant	6/7		XP_011511748.1
RNF212	NM_001366918.1	c.648-345G>A		intron_variant			NP_001353847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF212	ENST00000698262.1	c.804G>A	p.Arg268Arg	synonymous_variant	11/12			ENSP00000513634.1
RNF212	ENST00000505693.5	n.731G>A		non_coding_transcript_exon_variant	5/6	5
RNF212	ENST00000514024.5	n.264G>A		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32592 AN: 152048 Hom.: 6456 Cov.: 33

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0738

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0673

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0959

Gnomad OTH AF: 0.176

GnomAD4 exome AF: 0.0992 AC: 82856 AN: 835300 Hom.: 5970 Cov.: 27 AF XY: 0.0984 AC XY: 37962 AN XY: 385870

Gnomad4 AFR exome AF: 0.560

Gnomad4 AMR exome AF: 0.0877

Gnomad4 ASJ exome AF: 0.0735

Gnomad4 EAS exome AF: 0.000551

Gnomad4 SAS exome AF: 0.0782

Gnomad4 FIN exome AF: 0.0955

Gnomad4 NFE exome AF: 0.0906

Gnomad4 OTH exome AF: 0.106

GnomAD4 genome AF: 0.215 AC: 32644 AN: 152166 Hom.: 6469 Cov.: 33 AF XY: 0.210 AC XY: 15591 AN XY: 74396

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.0738

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0682

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.0959

Gnomad4 OTH AF: 0.173

Alfa AF: 0.149 Hom.: 613

Bravo AF: 0.228

Asia WGS AF: 0.0610 AC: 213 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

RNF212-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 10, 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	-0.48
CADD	Benign	3.6
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs60085185; hg19: chr4-1050636;