17-80353579-GGAGGTGGCA-G

Variant names:

• chr17-80353579-GGAGGTGGCA-G
• rs746722534
• NM_001256071.3:c.10505_10513delTGGCAGAGG

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM4 BS1

The NM_001256071.3(RNF213):​c.10505_10513delTGGCAGAGG​(p.Val3502_Glu3504del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,613,836 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: RNF213 NM_001256071.3 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.662
• Publications: 0 publications found

Genes affected

RNF213 (HGNC:14539): (ring finger protein 213) This gene encodes a protein containing a C3HC4-type RING finger domain, which is a specialized type of Zn-finger that binds two atoms of zinc and is thought to be involved in mediating protein-protein interactions. The protein also contains an AAA domain, which is associated with ATPase activity. This gene is a susceptibility gene for Moyamoya disease, a vascular disorder of intracranial arteries. This gene is also a translocation partner in anaplastic large cell lymphoma and inflammatory myofibroblastic tumor cases, where a t(2;17)(p23;q25) translocation has been identified with the anaplastic lymphoma kinase (ALK) gene on chromosome 2, and a t(8;17)(q24;q25) translocation has been identified with the MYC gene on chromosome 8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2011]

RNF213-AS1 (HGNC:54402): (RNF213 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001256071.3.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0000723 (11/152198) while in subpopulation AFR AF = 0.000145 (6/41454). AF 95% confidence interval is 0.0000628. There are 0 homozygotes in GnomAd4. There are 8 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256071.3. 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
	RNF213	NM_001256071.3	MANE Select	c.10505_10513delTGGCAGAGG	p.Val3502_Glu3504del	disruptive_inframe_deletion	Exon 34 of 68	NP_001243000.2	A0A0A0MTR7
	RNF213	NM_001410195.1		c.10652_10660delTGGCAGAGG	p.Val3551_Glu3553del	disruptive_inframe_deletion	Exon 35 of 69	NP_001397124.1	A0A0A0MTC1
	RNF213	NM_020914.5		c.10652_10660delTGGCAGAGG	p.Val3551_Glu3553del	disruptive_inframe_deletion	Exon 35 of 69	NP_065965.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF213	ENST00000582970.6	TSL:1 MANE Select	c.10505_10513delTGGCAGAGG	p.Val3502_Glu3504del	disruptive_inframe_deletion	Exon 34 of 68	ENSP00000464087.1	A0A0A0MTR7
	RNF213	ENST00000508628.6	TSL:5	c.10652_10660delTGGCAGAGG	p.Val3551_Glu3553del	disruptive_inframe_deletion	Exon 35 of 69	ENSP00000425956.2	A0A0A0MTC1
	RNF213-AS1	ENST00000575034.5	TSL:2	n.1891_1899delTGCCACCTC		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000440 AC: 11 AN: 249770 AF XY: 0.0000444

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000268

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000287 AC: 42 AN: 1461638 Hom.: 0 AF XY: 0.0000261 AC XY: 19 AN XY: 727120

African (AFR) AF: 0.000120 AC: 4 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39698

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1111804

Other (OTH) AF: 0.0000497 AC: 3 AN: 60390

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74336

African (AFR) AF: 0.000145 AC: 6 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000108 Hom.: 0

Bravo AF: 0.0000718

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.66
Mutation Taster		=159/41	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs746722534; hg19: chr17-78327379; COSMIC: COSV60391408; COSMIC: COSV60391408;