chr6-125044502-A-T

Variant names:

• chr6-125044502-A-T
• rs485640
• NM_001286398.3:c.883-709A>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.883-709A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 151,914 control chromosomes in the GnomAD database, including 15,518 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 0.45 (15518 hom., 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF217	NM_001286398.3	c.883-709A>T		intron_variant	Intron 1 of 5	ENST00000521654.7	NP_001273327.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF217	ENST00000521654.7	c.883-709A>T		intron_variant	Intron 1 of 5	2	NM_001286398.3	ENSP00000428698.2

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67850 AN: 151794 Hom.: 15507 Cov.: 32

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.447 AC: 67890 AN: 151914 Hom.: 15518 Cov.: 32 AF XY: 0.451 AC XY: 33491 AN XY: 74238

African (AFR) AF: 0.483 AC: 20023 AN: 41444

American (AMR) AF: 0.537 AC: 8184 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 914 AN: 3468

East Asian (EAS) AF: 0.517 AC: 2655 AN: 5134

South Asian (SAS) AF: 0.531 AC: 2556 AN: 4818

European-Finnish (FIN) AF: 0.396 AC: 4179 AN: 10554

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28126 AN: 67948

Other (OTH) AF: 0.418 AC: 883 AN: 2114

Alfa AF: 0.438 Hom.: 1838

Bravo AF: 0.456

Asia WGS AF: 0.514 AC: 1784 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.2
DANN	Benign	0.82
PhyloP100		0.58
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: rs485640; hg19: chr6-125365648;