rs2014318

chr4-1074990-A-Gchr4-1074990-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001131034.4(RNF212):c.511-1328T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 152,172 control chromosomes in the GnomAD database, including 50,728 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.81 (50728 hom., cov: 32)
• Consequence: RNF212 NM_001131034.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.407

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF212	NM_001131034.4	c.511-1328T>C		intron_variant		ENST00000433731.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF212	ENST00000433731.7	c.511-1328T>C		intron_variant		1	NM_001131034.4	A2

Frequencies

GnomAD3 genomes AF: 0.811 AC: 123297 AN: 152054 Hom.: 50692 Cov.: 32

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.804

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.793

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.811 AC: 123384 AN: 152172 Hom.: 50728 Cov.: 32 AF XY: 0.806 AC XY: 59974 AN XY: 74376

Gnomad4 AFR AF: 0.940

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.784

Gnomad4 EAS AF: 0.619

Gnomad4 SAS AF: 0.757

Gnomad4 FIN AF: 0.804

Gnomad4 NFE AF: 0.784

Gnomad4 OTH AF: 0.791

Alfa AF: 0.767 Hom.: 8413

Bravo AF: 0.806

Asia WGS AF: 0.667 AC: 2320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	1.6
Dann	Benign	0.44

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: rs2014318; hg19: chr4-1068778;