rs12051723

Positions:

• chr17-80350459-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF213	NM_001256071.3	c.10184+63G>T		intron_variant		ENST00000582970.6	NP_001243000.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF213	ENST00000582970.6	c.10184+63G>T		intron_variant		1	NM_001256071.3	ENSP00000464087	P2
RNF213	ENST00000508628.6	c.10331+63G>T		intron_variant		5		ENSP00000425956	A2

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

Gnomad4 AFR exome AF: 0.0207

Gnomad4 AMR exome AF: 0.0814

Gnomad4 ASJ exome AF: 0.156

Gnomad4 EAS exome AF: 0.198

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.142

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.135

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

Gnomad4 AFR AF: 0.0243

Gnomad4 AMR AF: 0.0984

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.243

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.121

Alfa AF: 0.132 Hom.: 1466

Bravo AF: 0.101

Asia WGS AF: 0.161 AC: 560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.5
DANN	Benign	0.73

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: rs12051723; hg19: chr17-78324259; COSMIC: COSV60393219; COSMIC: COSV60393219;