rs9321013

Positions:

• chr6-125009775-G-A
• chr6-125009775-G-T

Variant summary

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

The NM_001286398.3(RNF217):​c.883-35436G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 151,932 control chromosomes in the GnomAD database, including 5,540 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 0.26 (5540 hom., cov: 31)
• Consequence: RNF217 NM_001286398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF217	NM_001286398.3	c.883-35436G>A		intron_variant		ENST00000521654.7	NP_001273327.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF217	ENST00000521654.7	c.883-35436G>A		intron_variant		2	NM_001286398.3	ENSP00000428698	P1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38886 AN: 151810 Hom.: 5532 Cov.: 31

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.256 AC: 38909 AN: 151932 Hom.: 5540 Cov.: 31 AF XY: 0.258 AC XY: 19174 AN XY: 74222

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.259

Alfa AF: 0.253 Hom.: 2723

Bravo AF: 0.246

Asia WGS AF: 0.360 AC: 1254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.67

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: rs9321013; hg19: chr6-125330921;