rs11154284

Variant names:

• chr6-125017207-C-T
• rs11154284
• NM_001286398.3:c.883-28004C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286398.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF217	NM_001286398.3	MANE Select	c.883-28004C>T		intron	N/A	NP_001273327.1
	RNF217	NM_152553.5		c.6+7925C>T		intron	N/A	NP_689766.1
	RNF217	NR_104440.3		n.235+20552C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF217	ENST00000521654.7	TSL:2 MANE Select	c.883-28004C>T		intron	N/A	ENSP00000428698.2
	RNF217	ENST00000359704.2	TSL:1	c.6+7925C>T		intron	N/A	ENSP00000352734.2
	RNF217	ENST00000560949.5	TSL:5	c.100-28004C>T		intron	N/A	ENSP00000452812.2

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

African (AFR) AF: 0.526 AC: 21813 AN: 41502

American (AMR) AF: 0.611 AC: 9326 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2291 AN: 3472

East Asian (EAS) AF: 0.330 AC: 1699 AN: 5152

South Asian (SAS) AF: 0.647 AC: 3114 AN: 4816

European-Finnish (FIN) AF: 0.606 AC: 6387 AN: 10546

Middle Eastern (MID) AF: 0.637 AC: 186 AN: 292

European-Non Finnish (NFE) AF: 0.701 AC: 47643 AN: 67974

Other (OTH) AF: 0.626 AC: 1321 AN: 2110

Alfa AF: 0.676 Hom.: 21228

Bravo AF: 0.617

Asia WGS AF: 0.488 AC: 1695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.48
PhyloP100		-0.053
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11154284; hg19: chr6-125338353;