17-80353558-G-A

Variant names:

• chr17-80353558-G-A
• rs7216493
• NM_001256071.3:c.10470G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001256071.3(RNF213):​c.10470G>A​(p.Glu3490Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 1,613,234 control chromosomes in the GnomAD database, including 388,373 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (35645 hom., cov: 31)
  • Exomes 𝑓: 0.69 (352728 hom.)
• Consequence: RNF213 NM_001256071.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.668
• Publications: 30 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 17-80353558-G-A is Benign according to our data. Variant chr17-80353558-G-A is described in ClinVar as Benign. ClinVar VariationId is 1598973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.668 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

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.10470G>A	p.Glu3490Glu	synonymous	Exon 34 of 68	NP_001243000.2	A0A0A0MTR7
	RNF213	NM_001410195.1		c.10617G>A	p.Glu3539Glu	synonymous	Exon 35 of 69	NP_001397124.1	A0A0A0MTC1
	RNF213	NM_020914.5		c.10617G>A	p.Glu3539Glu	synonymous	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.10470G>A	p.Glu3490Glu	synonymous	Exon 34 of 68	ENSP00000464087.1	A0A0A0MTR7
	RNF213	ENST00000508628.6	TSL:5	c.10617G>A	p.Glu3539Glu	synonymous	Exon 35 of 69	ENSP00000425956.2	A0A0A0MTC1
	RNF213-AS1	ENST00000575034.5	TSL:2	n.1921C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103429 AN: 151866 Hom.: 35619 Cov.: 31

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.671

GnomAD2 exomes AF: 0.650 AC: 161455 AN: 248378 AF XY: 0.657

Gnomad AFR exome AF: 0.700

Gnomad AMR exome AF: 0.434

Gnomad ASJ exome AF: 0.733

Gnomad EAS exome AF: 0.522

Gnomad FIN exome AF: 0.735

Gnomad NFE exome AF: 0.714

Gnomad OTH exome AF: 0.678

GnomAD4 exome AF: 0.692 AC: 1010695 AN: 1461250 Hom.: 352728 Cov.: 55 AF XY: 0.691 AC XY: 502470 AN XY: 726872

African (AFR) AF: 0.705 AC: 23613 AN: 33476

American (AMR) AF: 0.446 AC: 19848 AN: 44530

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 19084 AN: 26134

East Asian (EAS) AF: 0.512 AC: 20322 AN: 39674

South Asian (SAS) AF: 0.616 AC: 53122 AN: 86210

European-Finnish (FIN) AF: 0.736 AC: 39300 AN: 53398

Middle Eastern (MID) AF: 0.735 AC: 4237 AN: 5768

European-Non Finnish (NFE) AF: 0.710 AC: 789444 AN: 1111676

Other (OTH) AF: 0.691 AC: 41725 AN: 60384

GnomAD4 genome AF: 0.681 AC: 103497 AN: 151984 Hom.: 35645 Cov.: 31 AF XY: 0.676 AC XY: 50191 AN XY: 74266

African (AFR) AF: 0.695 AC: 28775 AN: 41420

American (AMR) AF: 0.553 AC: 8451 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 2530 AN: 3468

East Asian (EAS) AF: 0.521 AC: 2688 AN: 5160

South Asian (SAS) AF: 0.609 AC: 2934 AN: 4814

European-Finnish (FIN) AF: 0.734 AC: 7762 AN: 10572

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.709 AC: 48171 AN: 67970

Other (OTH) AF: 0.666 AC: 1402 AN: 2104

Alfa AF: 0.696 Hom.: 130223

Bravo AF: 0.667

Asia WGS AF: 0.584 AC: 2032 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.34
DANN	Benign	0.84
PhyloP100		-0.67
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: rs7216493; hg19: chr17-78327358; COSMIC: COSV60388865; COSMIC: COSV60388865;