4-1056865-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.787C>T(p.Pro263Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 987,636 control chromosomes in the GnomAD database, including 313,479 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 0.84 (54593 hom., cov: 32)
  • Exomes 𝑓: 0.79 (258886 hom.)
• Consequence: RNF212 NM_001366919.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0720

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=-0.84).
• BP6: Variant 4-1056865-G-A is Benign according to our data. Variant chr4-1056865-G-A is described in ClinVar as [Benign]. Clinvar id is 3047718.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF212	NM_001366919.1	c.787C>T	p.Pro263Ser	missense_variant	11/12
RNF212	XM_047450083.1	c.685C>T	p.Pro229Ser	missense_variant	9/10
RNF212	XM_011513446.2	c.523C>T	p.Pro175Ser	missense_variant	6/7
RNF212	NM_001366918.1	c.648-362C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF212	ENST00000698262.1	c.787C>T	p.Pro263Ser	missense_variant	11/12			P2
RNF212	ENST00000505693.5	n.714C>T		non_coding_transcript_exon_variant	5/6	5
RNF212	ENST00000514024.5	n.247C>T		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes AF: 0.843 AC: 128188 AN: 152042 Hom.: 54539 Cov.: 32

Gnomad AFR AF: 0.960

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.826

GnomAD4 exome AF: 0.787 AC: 657236 AN: 835476 Hom.: 258886 Cov.: 34 AF XY: 0.786 AC XY: 303256 AN XY: 385954

Gnomad4 AFR exome AF: 0.973

Gnomad4 AMR exome AF: 0.877

Gnomad4 ASJ exome AF: 0.802

Gnomad4 EAS exome AF: 0.745

Gnomad4 SAS exome AF: 0.784

Gnomad4 FIN exome AF: 0.785

Gnomad4 NFE exome AF: 0.783

Gnomad4 OTH exome AF: 0.787

GnomAD4 genome AF: 0.843 AC: 128303 AN: 152160 Hom.: 54593 Cov.: 32 AF XY: 0.843 AC XY: 62693 AN XY: 74384

Gnomad4 AFR AF: 0.960

Gnomad4 AMR AF: 0.862

Gnomad4 ASJ AF: 0.806

Gnomad4 EAS AF: 0.734

Gnomad4 SAS AF: 0.777

Gnomad4 FIN AF: 0.811

Gnomad4 NFE AF: 0.791

Gnomad4 OTH AF: 0.825

Alfa AF: 0.843 Hom.: 9297

Bravo AF: 0.852

Asia WGS AF: 0.724 AC: 2520 AN: 3478

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	-0.84
Cadd	Benign	0.16
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: rs3816474; hg19: chr4-1050653;