rs1322633

chr6-125082133-A-Gchr6-125082133-A-T

Variant summary

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

The NM_001286398.3(RNF217):c.1555+626A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 152,042 control chromosomes in the GnomAD database, including 9,027 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 0.31 (9027 hom., cov: 32)
• Consequence: RNF217 NM_001286398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF217	NM_001286398.3	c.1555+626A>G		intron_variant		ENST00000521654.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF217	ENST00000521654.7	c.1555+626A>G		intron_variant		2	NM_001286398.3	P1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46493 AN: 151922 Hom.: 9031 Cov.: 32

Gnomad AFR AF: 0.0854

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.306 AC: 46488 AN: 152042 Hom.: 9027 Cov.: 32 AF XY: 0.300 AC XY: 22303 AN XY: 74318

Gnomad4 AFR AF: 0.0855

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.495

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.344

Alfa AF: 0.421 Hom.: 24819

Bravo AF: 0.290

Asia WGS AF: 0.196 AC: 684 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.051
Dann	Benign	0.40

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: rs1322633; hg19: chr6-125403279; COSMIC: COSV51575315;