rs4045481

chr4-1096837-G-A

Variant summary

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

The NM_001131034.4(RNF212):c.174C>T(p.Thr58=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 1,601,476 control chromosomes in the GnomAD database, including 353,627 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.58 (27016 hom., cov: 33)
  • Exomes 𝑓: 0.67 (326611 hom.)
• Consequence: RNF212 NM_001131034.4 splice_region, synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.10

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=-1.05).
• BP6: Variant 4-1096837-G-A is Benign according to our data. Variant chr4-1096837-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-5.1 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF212	NM_001131034.4	c.174C>T	p.Thr58=	splice_region_variant, synonymous_variant	3/10	ENST00000433731.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF212	ENST00000433731.7	c.174C>T	p.Thr58=	splice_region_variant, synonymous_variant	3/10	1	NM_001131034.4	A2

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87681 AN: 152036 Hom.: 27022 Cov.: 33

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.605

GnomAD3 exomes AF: 0.637 AC: 160157 AN: 251362 Hom.: 52296 AF XY: 0.649 AC XY: 88164 AN XY: 135848

Gnomad AFR exome AF: 0.339

Gnomad AMR exome AF: 0.545

Gnomad ASJ exome AF: 0.718

Gnomad EAS exome AF: 0.617

Gnomad SAS exome AF: 0.690

Gnomad FIN exome AF: 0.677

Gnomad NFE exome AF: 0.681

Gnomad OTH exome AF: 0.655

GnomAD4 exome AF: 0.667 AC: 967293 AN: 1449322 Hom.: 326611 Cov.: 31 AF XY: 0.670 AC XY: 483352 AN XY: 721776

Gnomad4 AFR exome AF: 0.333

Gnomad4 AMR exome AF: 0.548

Gnomad4 ASJ exome AF: 0.716

Gnomad4 EAS exome AF: 0.576

Gnomad4 SAS exome AF: 0.692

Gnomad4 FIN exome AF: 0.678

Gnomad4 NFE exome AF: 0.683

Gnomad4 OTH exome AF: 0.651

GnomAD4 genome AF: 0.576 AC: 87698 AN: 152154 Hom.: 27016 Cov.: 33 AF XY: 0.578 AC XY: 43001 AN XY: 74382

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.564

Gnomad4 ASJ AF: 0.720

Gnomad4 EAS AF: 0.619

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.678

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.605

Alfa AF: 0.658 Hom.: 50422

Bravo AF: 0.554

Asia WGS AF: 0.605 AC: 2102 AN: 3478

EpiCase AF: 0.674

EpiControl AF: 0.671

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.0090
Dann	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs4045481; hg19: chr4-1090625; COSMIC: COSV61363712; COSMIC: COSV61363712;