Variant 17-80273365-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001256071.3(RNF213):c.222C>T(p.Pro74=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0064 in 1,613,196 control chromosomes in the GnomAD database, including 624 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.034 ( 322 hom., cov: 31)

Exomes 𝑓: 0.0035 ( 302 hom. )

Consequence

RNF213
NM_001256071.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.07

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 17-80273365-C-T is Benign according to our data. Variant chr17-80273365-C-T is described in ClinVar as [Benign]. Clinvar id is 1598585.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.07 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF213	NM_001256071.3 linkuse as main transcript	c.222C>T	p.Pro74=	synonymous_variant	3/68	ENST00000582970.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF213	ENST00000582970.6 linkuse as main transcript	c.222C>T	p.Pro74=	synonymous_variant	3/68	1	NM_001256071.3	P2
RNF213	ENST00000319921.4 linkuse as main transcript	c.222C>T	p.Pro74=	synonymous_variant	3/17	1			Q63HN8-5
RNF213	ENST00000508628.6 linkuse as main transcript	c.222C>T	p.Pro74=	synonymous_variant	3/69	5		A2

Frequencies

GnomAD3 genomes

AF:

0.0343

AC:

5217

AN:

152046

Hom.:

322

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0112

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:

0.000397

Gnomad OTH

AF:

0.0201

GnomAD3 exomes

AF:

0.00885

AC:

2214

AN:

250136

Hom.:

123

AF XY:

0.00651

AC XY:

884

AN XY:

135716

show subpopulations

Gnomad AFR exome

AF:

0.123

Gnomad AMR exome

AF:

0.00471

Gnomad ASJ exome

AF:

0.000500

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000328

Gnomad OTH exome

AF:

0.00377

GnomAD4 exome

AF:

0.00349

AC:

5098

AN:

1461032

Hom.:

302

Cov.:

AF XY:

0.00296

AC XY:

2153

AN XY:

726770

show subpopulations

Gnomad4 AFR exome

AF:

0.124

Gnomad4 AMR exome

AF:

0.00577

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000182

Gnomad4 OTH exome

AF:

0.00717

GnomAD4 genome

AF:

0.0343

AC:

5223

AN:

152164

Hom.:

322

Cov.:

AF XY:

0.0334

AC XY:

2482

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.120

Gnomad4 AMR

AF:

0.0112

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.0199

Alfa

AF:

0.0152

Hom.:

Bravo

AF:

0.0390

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 14, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.85

DANN

Benign

0.55

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over