rs1322633

Variant names:

• chr6-125082133-A-G
• rs1322633
• NM_001286398.3:c.1555+626A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-125082133-A-G
• chr6-125082133-A-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.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
• Publications: 7 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 (NFE) allele frequency at 95% confidence interval = 0.44 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF217	NM_001286398.3	MANE Select	c.1555+626A>G		intron	N/A	NP_001273327.1
	RNF217	NM_152553.5		c.680-316A>G		intron	N/A	NP_689766.1
	RNF217	NR_104440.3		n.908+626A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF217	ENST00000521654.7	TSL:2 MANE Select	c.1555+626A>G		intron	N/A	ENSP00000428698.2
	RNF217	ENST00000359704.2	TSL:1	c.680-316A>G		intron	N/A	ENSP00000352734.2
	RNF217	ENST00000560949.5	TSL:5	c.773-316A>G		intron	N/A	ENSP00000452812.2

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

African (AFR) AF: 0.0855 AC: 3549 AN: 41532

American (AMR) AF: 0.262 AC: 3989 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1716 AN: 3470

East Asian (EAS) AF: 0.145 AC: 748 AN: 5168

South Asian (SAS) AF: 0.254 AC: 1228 AN: 4828

European-Finnish (FIN) AF: 0.356 AC: 3757 AN: 10568

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30165 AN: 67928

Other (OTH) AF: 0.344 AC: 727 AN: 2112

Alfa AF: 0.394 Hom.: 38654

Bravo AF: 0.290

Asia WGS AF: 0.196 AC: 684 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.051
DANN	Benign	0.40
PhyloP100		-1.7
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: rs1322633; hg19: chr6-125403279; COSMIC: COSV51575315;