chr17-80374694-A-G

Variant names:

• chr17-80374694-A-G
• rs6565681
• NM_001256071.3:c.13074+105A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001256071.3(RNF213):​c.13074+105A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 1,352,698 control chromosomes in the GnomAD database, including 454,532 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 0.82 (51861 hom., cov: 31)
  • Exomes 𝑓: 0.82 (402671 hom.)
• Consequence: RNF213 NM_001256071.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.524
• Publications: 36 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF213	NM_001256071.3	c.13074+105A>G		intron_variant	Intron 50 of 67	ENST00000582970.6	NP_001243000.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF213	ENST00000582970.6	c.13074+105A>G		intron_variant	Intron 50 of 67	1	NM_001256071.3	ENSP00000464087.1

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124688 AN: 151966 Hom.: 51821 Cov.: 31

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.818

GnomAD2 exomes AF: 0.757 AC: 127806 AN: 168874 AF XY: 0.760

Gnomad AFR exome AF: 0.898

Gnomad AMR exome AF: 0.551

Gnomad ASJ exome AF: 0.854

Gnomad EAS exome AF: 0.580

Gnomad FIN exome AF: 0.817

Gnomad NFE exome AF: 0.841

Gnomad OTH exome AF: 0.797

GnomAD4 exome AF: 0.815 AC: 978561 AN: 1200614 Hom.: 402671 Cov.: 15 AF XY: 0.812 AC XY: 488864 AN XY: 602218

African (AFR) AF: 0.901 AC: 25061 AN: 27826

American (AMR) AF: 0.564 AC: 20502 AN: 36364

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 20277 AN: 23692

East Asian (EAS) AF: 0.556 AC: 19324 AN: 34768

South Asian (SAS) AF: 0.694 AC: 52760 AN: 75980

European-Finnish (FIN) AF: 0.818 AC: 36760 AN: 44960

Middle Eastern (MID) AF: 0.833 AC: 4068 AN: 4882

European-Non Finnish (NFE) AF: 0.842 AC: 758250 AN: 900852

Other (OTH) AF: 0.810 AC: 41559 AN: 51290

GnomAD4 genome AF: 0.820 AC: 124769 AN: 152084 Hom.: 51861 Cov.: 31 AF XY: 0.811 AC XY: 60301 AN XY: 74332

African (AFR) AF: 0.895 AC: 37148 AN: 41504

American (AMR) AF: 0.664 AC: 10159 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.855 AC: 2967 AN: 3472

East Asian (EAS) AF: 0.575 AC: 2950 AN: 5126

South Asian (SAS) AF: 0.677 AC: 3262 AN: 4818

European-Finnish (FIN) AF: 0.817 AC: 8631 AN: 10570

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.838 AC: 56997 AN: 67990

Other (OTH) AF: 0.813 AC: 1716 AN: 2110

Alfa AF: 0.825 Hom.: 247093

Bravo AF: 0.812

Asia WGS AF: 0.629 AC: 2188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.33
DANN	Benign	0.29
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6565681; hg19: chr17-78348494;