Variant chr17-80353558-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001256071.3(RNF213):c.10470G>A(p.Glu3490Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 1,613,234 control chromosomes in the GnomAD database, including 388,373 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 35645 hom., cov: 31)

Exomes 𝑓: 0.69 ( 352728 hom. )

Consequence

RNF213
NM_001256071.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.668

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:

RNF213-AS1 (HGNC:):

RNF213-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 17-80353558-G-A is Benign according to our data. Variant chr17-80353558-G-A is described in ClinVar as [Benign]. Clinvar id is 1598973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80353558-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.668 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF213	NM_001256071.3 linkuse as main transcript	c.10470G>A	p.Glu3490Glu	synonymous_variant	34/68	ENST00000582970.6	NP_001243000.2	Q63HN8A0A0A0MTR7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RNF213	ENST00000582970.6 linkuse as main transcript	c.10470G>A	p.Glu3490Glu	synonymous_variant	34/68	1	NM_001256071.3	ENSP00000464087.1	A0A0A0MTR7
RNF213	ENST00000508628.6 linkuse as main transcript	c.10617G>A	p.Glu3539Glu	synonymous_variant	35/69	5		ENSP00000425956.2	A0A0A0MTC1
RNF213-AS1	ENST00000575034.5 linkuse as main transcript	n.1921C>T		non_coding_transcript_exon_variant	2/2	2
RNF213-AS1	ENST00000613190.1 linkuse as main transcript	n.254C>T		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes

AF:

0.681

AC:

103429

AN:

151866

Hom.:

35619

Cov.:

show subpopulations

Gnomad AFR

AF:

0.694

Gnomad AMI

AF:

0.618

Gnomad AMR

AF:

0.555

Gnomad ASJ

AF:

0.730

Gnomad EAS

AF:

0.520

Gnomad SAS

AF:

0.610

Gnomad FIN

AF:

0.734

Gnomad MID

AF:

0.750

Gnomad NFE

AF:

0.709

Gnomad OTH

AF:

0.671

GnomAD3 exomes

AF:

0.650

AC:

161455

AN:

248378

Hom.:

53953

AF XY:

0.657

AC XY:

88323

AN XY:

134376

show subpopulations

Gnomad AFR exome

AF:

0.700

Gnomad AMR exome

AF:

0.434

Gnomad ASJ exome

AF:

0.733

Gnomad EAS exome

AF:

0.522

Gnomad SAS exome

AF:

0.618

Gnomad FIN exome

AF:

0.735

Gnomad NFE exome

AF:

0.714

Gnomad OTH exome

AF:

0.678

GnomAD4 exome

AF:

0.692

AC:

1010695

AN:

1461250

Hom.:

352728

Cov.:

AF XY:

0.691

AC XY:

502470

AN XY:

726872

show subpopulations

Gnomad4 AFR exome

AF:

0.705

Gnomad4 AMR exome

AF:

0.446

Gnomad4 ASJ exome

AF:

0.730

Gnomad4 EAS exome

AF:

0.512

Gnomad4 SAS exome

AF:

0.616

Gnomad4 FIN exome

AF:

0.736

Gnomad4 NFE exome

AF:

0.710

Gnomad4 OTH exome

AF:

0.691

GnomAD4 genome

AF:

0.681

AC:

103497

AN:

151984

Hom.:

35645

Cov.:

AF XY:

0.676

AC XY:

50191

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.695

Gnomad4 AMR

AF:

0.553

Gnomad4 ASJ

AF:

0.730

Gnomad4 EAS

AF:

0.521

Gnomad4 SAS

AF:

0.609

Gnomad4 FIN

AF:

0.734

Gnomad4 NFE

AF:

0.709

Gnomad4 OTH

AF:

0.666

Alfa

AF:

0.702

Hom.:

54978

Bravo

AF:

0.667

Asia WGS

AF:

0.584

AC:

2032

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.34

DANN

Benign

0.84

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