Variant 17-80287795-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001256071.3(RNF213):c.262-20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00743 in 1,611,950 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0077 ( 50 hom. )

Consequence

RNF213
NM_001256071.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0540

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 17-80287795-G-A is Benign according to our data. Variant chr17-80287795-G-A is described in ClinVar as [Benign]. Clinvar id is 1613400.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00482 (734/152326) while in subpopulation NFE AF= 0.00782 (532/68030). AF 95% confidence interval is 0.00727. There are 3 homozygotes in gnomad4. There are 321 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF213	NM_001256071.3 linkuse as main transcript	c.262-20G>A		intron_variant		ENST00000582970.6

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
RNF213	ENST00000582970.6 linkuse as main transcript	c.262-20G>A	intron_variant	1	NM_001256071.3	P2
RNF213	ENST00000319921.4 linkuse as main transcript	c.262-20G>A	intron_variant	1			Q63HN8-5
RNF213	ENST00000508628.6 linkuse as main transcript	c.409-20G>A	intron_variant	5		A2

Frequencies

GnomAD3 genomes

AF:

0.00482

AC:

734

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00130

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00608

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00782

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00454

AC:

1132

AN:

249302

Hom.:

AF XY:

0.00461

AC XY:

622

AN XY:

135054

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00240

Gnomad ASJ exome

AF:

0.00695

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00193

Gnomad FIN exome

AF:

0.00194

Gnomad NFE exome

AF:

0.00738

Gnomad OTH exome

AF:

0.00490

GnomAD4 exome

AF:

0.00771

AC:

11248

AN:

1459624

Hom.:

Cov.:

AF XY:

0.00743

AC XY:

5398

AN XY:

726258

show subpopulations

Gnomad4 AFR exome

AF:

0.00138

Gnomad4 AMR exome

AF:

0.00255

Gnomad4 ASJ exome

AF:

0.00647

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00194

Gnomad4 FIN exome

AF:

0.00158

Gnomad4 NFE exome

AF:

0.00921

Gnomad4 OTH exome

AF:

0.00711

GnomAD4 genome

AF:

0.00482

AC:

734

AN:

152326

Hom.:

Cov.:

AF XY:

0.00431

AC XY:

321

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00130

Gnomad4 AMR

AF:

0.00608

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.00782

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00596

Hom.:

Bravo

AF:

0.00476

Asia WGS

AF:

0.000866

AC:

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	Jan 13, 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

-0.87

CADD

Benign

3.9

DANN

Benign

0.32

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