chr17-80354076-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_001256071.3(RNF213):​c.10636A>G​(p.Met3546Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,614,066 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000072 ( 1 hom. )

Consequence

RNF213
NM_001256071.3 missense

Scores

4
14

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.40
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]
RNF213-AS1 (HGNC:54402): (RNF213 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.019533157).
BP6
Variant 17-80354076-A-G is Benign according to our data. Variant chr17-80354076-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 710512.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000564 (86/152358) while in subpopulation AFR AF= 0.0018 (75/41590). AF 95% confidence interval is 0.00147. There are 0 homozygotes in gnomad4. There are 45 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RNF213NM_001256071.3 linkc.10636A>G p.Met3546Val missense_variant Exon 35 of 68 ENST00000582970.6 NP_001243000.2 Q63HN8A0A0A0MTR7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RNF213ENST00000582970.6 linkc.10636A>G p.Met3546Val missense_variant Exon 35 of 68 1 NM_001256071.3 ENSP00000464087.1 A0A0A0MTR7
RNF213ENST00000508628.6 linkc.10783A>G p.Met3595Val missense_variant Exon 36 of 69 5 ENSP00000425956.2 A0A0A0MTC1
RNF213-AS1ENST00000575034.5 linkn.1403T>C non_coding_transcript_exon_variant Exon 2 of 2 2
RNF213ENST00000558116.5 linkn.-36A>G upstream_gene_variant 2

Frequencies

GnomAD3 genomes
AF:
0.000565
AC:
86
AN:
152240
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00181
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000392
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000201
AC:
50
AN:
248916
Hom.:
1
AF XY:
0.000156
AC XY:
21
AN XY:
134900
show subpopulations
Gnomad AFR exome
AF:
0.00222
Gnomad AMR exome
AF:
0.000376
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000898
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000718
AC:
105
AN:
1461708
Hom.:
1
Cov.:
32
AF XY:
0.0000688
AC XY:
50
AN XY:
727168
show subpopulations
Gnomad4 AFR exome
AF:
0.00194
Gnomad4 AMR exome
AF:
0.000358
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000188
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.000199
GnomAD4 genome
AF:
0.000564
AC:
86
AN:
152358
Hom.:
0
Cov.:
32
AF XY:
0.000604
AC XY:
45
AN XY:
74512
show subpopulations
Gnomad4 AFR
AF:
0.00180
Gnomad4 AMR
AF:
0.000392
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000120
Hom.:
0
Bravo
AF:
0.000570
ESP6500AA
AF:
0.00204
AC:
9
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000231
AC:
28

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jan 30, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
14
DANN
Benign
0.42
DEOGEN2
Benign
0.22
T;T
Eigen
Benign
-0.61
Eigen_PC
Benign
-0.67
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.65
T;T
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.020
T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.48
T
PROVEAN
Uncertain
-3.5
D;.
REVEL
Benign
0.14
Sift
Uncertain
0.016
D;.
Sift4G
Uncertain
0.0030
D;D
Vest4
0.35
MVP
0.30
MPC
0.58
ClinPred
0.070
T
GERP RS
-2.2
RBP_binding_hub_radar
1.1
RBP_regulation_power_radar
2.8

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: rs148653181; hg19: chr17-78327876; API