rs12051723

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.345
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 UniProt
RNF213NM_001256071.3 linkuse as main transcriptc.10184+63G>T intron_variant ENST00000582970.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNF213ENST00000582970.6 linkuse as main transcriptc.10184+63G>T intron_variant 1 NM_001256071.3 P2
RNF213ENST00000508628.6 linkuse as main transcriptc.10331+63G>T intron_variant 5 A2

Frequencies

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

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