rs11154284

Positions:

• chr6-125017207-C-T

Variant summary

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

The NM_001286398.3(RNF217):​c.883-28004C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 152,044 control chromosomes in the GnomAD database, including 30,064 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 0.62 (30064 hom., cov: 33)
• Consequence: RNF217 NM_001286398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530

Genes affected

RNF217 (HGNC:21487): (ring finger protein 217) This protein encoded by this gene is a member of the RING1-IBR-RING24 (RBR) ubiquitin protein ligase family, and it belongs to a subfamily of these proteins that contain a transmembrane domain. This protein can interact with the HAX1 anti-apoptotic protein via its C-terminal RING finger motif, which suggests a role in apoptosis signaling. It is thought that deregulation of this gene can be a mechanism in leukemogenesis. Mutations in the region encoding the protein GXXXG motif, which appears to be necessary for protein self-association, have been found in human cancers. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2016]

RNF217 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF217	NM_001286398.3	c.883-28004C>T		intron_variant		ENST00000521654.7	NP_001273327.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF217	ENST00000521654.7	c.883-28004C>T		intron_variant		2	NM_001286398.3	ENSP00000428698.2

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94380 AN: 151926 Hom.: 30042 Cov.: 33

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.659

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.633

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

GnomAD4 genome AF: 0.621 AC: 94448 AN: 152044 Hom.: 30064 Cov.: 33 AF XY: 0.615 AC XY: 45693 AN XY: 74280

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.611

Gnomad4 ASJ AF: 0.660

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.647

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.626

Alfa AF: 0.676 Hom.: 19279

Bravo AF: 0.617

Asia WGS AF: 0.488 AC: 1695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.48

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: rs11154284; hg19: chr6-125338353;