rs485640

Variant names:

• chr6-125044502-A-C
• rs485640
• NM_001286398.3:c.883-709A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-125044502-A-C
• chr6-125044502-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001286398.3(RNF217):​c.883-709A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: RNF217 NM_001286398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.582
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF217	NM_001286398.3	MANE Select	c.883-709A>C		intron	N/A	NP_001273327.1	Q8TC41-1
	RNF217	NM_152553.5		c.7-709A>C		intron	N/A	NP_689766.1	Q8TC41-2
	RNF217	NR_104440.3		n.236-709A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF217	ENST00000521654.7	TSL:2 MANE Select	c.883-709A>C		intron	N/A	ENSP00000428698.2	Q8TC41-1
	RNF217	ENST00000359704.2	TSL:1	c.7-709A>C		intron	N/A	ENSP00000352734.2	Q8TC41-2
	RNF217	ENST00000560949.5	TSL:5	c.100-709A>C		intron	N/A	ENSP00000452812.2	H0YKH8

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.68
PhyloP100		0.58

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: rs485640; hg19: chr6-125365648;