4-1093477-T-C

Variant summary

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

The NM_001131034.4(RNF212):c.247-2639A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 1,449,300 control chromosomes in the GnomAD database, including 440,015 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.81 (50998 hom., cov: 32)
  • Exomes 𝑓: 0.77 (389017 hom.)
• Consequence: RNF212 NM_001131034.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.60

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 (MetaRNN=1.5909047E-6).
• BP6: Variant 4-1093477-T-C is Benign according to our data. Variant chr4-1093477-T-C is described in ClinVar as [Benign]. Clinvar id is 1222937.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-1093477-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF212	NM_001131034.4	c.247-2639A>G		intron_variant		ENST00000433731.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF212	ENST00000433731.7	c.247-2639A>G		intron_variant		1	NM_001131034.4	A2

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123568 AN: 152022 Hom.: 50959 Cov.: 32

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.804

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.795

GnomAD3 exomes AF: 0.712 AC: 53742 AN: 75470 Hom.: 19589 AF XY: 0.707 AC XY: 27981 AN XY: 39596

Gnomad AFR exome AF: 0.949

Gnomad AMR exome AF: 0.600

Gnomad ASJ exome AF: 0.712

Gnomad EAS exome AF: 0.611

Gnomad SAS exome AF: 0.681

Gnomad FIN exome AF: 0.754

Gnomad NFE exome AF: 0.745

Gnomad OTH exome AF: 0.710

GnomAD4 exome AF: 0.772 AC: 1001750 AN: 1297160 Hom.: 389017 Cov.: 38 AF XY: 0.771 AC XY: 486205 AN XY: 630502

Gnomad4 AFR exome AF: 0.952

Gnomad4 AMR exome AF: 0.625

Gnomad4 ASJ exome AF: 0.774

Gnomad4 EAS exome AF: 0.573

Gnomad4 SAS exome AF: 0.757

Gnomad4 FIN exome AF: 0.788

Gnomad4 NFE exome AF: 0.778

Gnomad4 OTH exome AF: 0.769

GnomAD4 genome AF: 0.813 AC: 123660 AN: 152140 Hom.: 50998 Cov.: 32 AF XY: 0.808 AC XY: 60071 AN XY: 74348

Gnomad4 AFR AF: 0.947

Gnomad4 AMR AF: 0.685

Gnomad4 ASJ AF: 0.785

Gnomad4 EAS AF: 0.618

Gnomad4 SAS AF: 0.758

Gnomad4 FIN AF: 0.804

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.794

Alfa AF: 0.783 Hom.: 39231

Bravo AF: 0.808

TwinsUK AF: 0.772 AC: 2861

ALSPAC AF: 0.767 AC: 2955

ExAC AF: 0.697 AC: 12019

Asia WGS AF: 0.667 AC: 2322 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 19, 2019

This variant is associated with the following publications: (PMID: 30679340) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.28
Dann	Benign	0.32
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00034	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.0000016	T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	1.0	P;P;P
PROVEAN	Benign	0.10	N
REVEL	Benign	0.069
Sift	Benign	1.0	T
Vest4		0.013
ClinPred		0.0080	T
GERP RS		-2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1670534; hg19: chr4-1087265; COSMIC: COSV61364340; COSMIC: COSV61364340;