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4-1056848-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001366919.1(RNF212):c.804G>A(p.Arg268=) 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 (★).

Frequency

Genomes: 𝑓 0.21 ( 6469 hom., cov: 33)
Exomes 𝑓: 0.099 ( 5970 hom. )

Consequence

RNF212
NM_001366919.1 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.144
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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 criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.144 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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 UniProt
RNF212NM_001366919.1 linkuse as main transcriptc.804G>A p.Arg268= synonymous_variant 11/12
RNF212XM_047450083.1 linkuse as main transcriptc.702G>A p.Arg234= synonymous_variant 9/10
RNF212XM_011513446.2 linkuse as main transcriptc.540G>A p.Arg180= synonymous_variant 6/7
RNF212NM_001366918.1 linkuse as main transcriptc.648-345G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNF212ENST00000698262.1 linkuse as main transcriptc.804G>A p.Arg268= synonymous_variant 11/12 P2
RNF212ENST00000505693.5 linkuse as main transcriptn.731G>A non_coding_transcript_exon_variant 5/65
RNF212ENST00000514024.5 linkuse as main transcriptn.264G>A non_coding_transcript_exon_variant 2/32

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.214
AC:
32592
AN:
152048
Hom.:
6456
Cov.:
33
show subpopulations
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
show subpopulations
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.215
AC:
32644
AN:
152166
Hom.:
6469
Cov.:
33
AF XY:
0.210
AC XY:
15591
AN XY:
74396
show subpopulations
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: criteria provided, single submitter
LINK: link

Submissions by phenotype

RNF212-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesMar 10, 2022This 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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs60085185; hg19: chr4-1050636; API