rs12051723

Variant names:

• chr17-80350459-G-T
• rs12051723
• NM_001256071.3:c.10184+63G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001256071.3(RNF213):​c.10184+63G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,057,972 control chromosomes in the GnomAD database, including 9,535 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 0.11 (1163 hom., cov: 33)
  • Exomes 𝑓: 0.13 (8372 hom.)
• Consequence: RNF213 NM_001256071.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.345
• Publications: 12 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 Gene-Disease associations (from GenCC):

• Moyamoya disease 2

  Inheritance: AD, AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.232 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.10184+63G>T		intron	N/A	NP_001243000.2	A0A0A0MTR7
	RNF213	NM_001410195.1		c.10331+63G>T		intron	N/A	NP_001397124.1	A0A0A0MTC1
	RNF213	NM_020914.5		c.10331+63G>T		intron	N/A	NP_065965.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF213	ENST00000582970.6	TSL:1 MANE Select	c.10184+63G>T		intron	N/A	ENSP00000464087.1	A0A0A0MTR7
	RNF213	ENST00000508628.6	TSL:5	c.10331+63G>T		intron	N/A	ENSP00000425956.2	A0A0A0MTC1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16446 AN: 152030 Hom.: 1164 Cov.: 33

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0986

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.119

GnomAD4 exome AF: 0.130 AC: 117460 AN: 905824 Hom.: 8372 AF XY: 0.131 AC XY: 61824 AN XY: 471594

African (AFR) AF: 0.0207 AC: 471 AN: 22738

American (AMR) AF: 0.0814 AC: 3321 AN: 40798

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 3533 AN: 22580

East Asian (EAS) AF: 0.198 AC: 7287 AN: 36778

South Asian (SAS) AF: 0.120 AC: 8844 AN: 73610

European-Finnish (FIN) AF: 0.142 AC: 6738 AN: 47468

Middle Eastern (MID) AF: 0.103 AC: 487 AN: 4748

European-Non Finnish (NFE) AF: 0.132 AC: 81104 AN: 615056

Other (OTH) AF: 0.135 AC: 5675 AN: 42048

GnomAD4 genome AF: 0.108 AC: 16445 AN: 152148 Hom.: 1163 Cov.: 33 AF XY: 0.108 AC XY: 8042 AN XY: 74370

African (AFR) AF: 0.0243 AC: 1007 AN: 41522

American (AMR) AF: 0.0984 AC: 1503 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 519 AN: 3472

East Asian (EAS) AF: 0.243 AC: 1258 AN: 5176

South Asian (SAS) AF: 0.127 AC: 613 AN: 4826

European-Finnish (FIN) AF: 0.145 AC: 1528 AN: 10568

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9622 AN: 67986

Other (OTH) AF: 0.121 AC: 256 AN: 2114

Alfa AF: 0.120 Hom.: 2187

Bravo AF: 0.101

Asia WGS AF: 0.161 AC: 560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.5
DANN	Benign	0.73
PhyloP100		0.34
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: rs12051723; hg19: chr17-78324259; COSMIC: COSV60393219; COSMIC: COSV60393219;