17-80374694-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. Variant has been reported in Lovd as Benign (no stars).

• 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

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 17-80374694-A-G is Benign according to our data. Variant chr17-80374694-A-G is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
RNF213	NM_001256071.3	c.13074+105A>G		intron_variant		ENST00000582970.6
RNF213-AS1	NR_029376.1	n.241-19406T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF213	ENST00000582970.6	c.13074+105A>G		intron_variant		1	NM_001256071.3	P2
RNF213-AS1	ENST00000575034.5	n.191-19406T>C		intron_variant, non_coding_transcript_variant		2

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

GnomAD3 exomes AF: 0.757 AC: 127806 AN: 168874 Hom.: 49706 AF XY: 0.760 AC XY: 68635 AN XY: 90344

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 SAS exome AF: 0.696

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

Gnomad4 AFR exome AF: 0.901

Gnomad4 AMR exome AF: 0.564

Gnomad4 ASJ exome AF: 0.856

Gnomad4 EAS exome AF: 0.556

Gnomad4 SAS exome AF: 0.694

Gnomad4 FIN exome AF: 0.818

Gnomad4 NFE exome AF: 0.842

Gnomad4 OTH exome AF: 0.810

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

Gnomad4 AFR AF: 0.895

Gnomad4 AMR AF: 0.664

Gnomad4 ASJ AF: 0.855

Gnomad4 EAS AF: 0.575

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.817

Gnomad4 NFE AF: 0.838

Gnomad4 OTH AF: 0.813

Alfa AF: 0.825 Hom.: 121817

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs6565681; hg19: chr17-78348494;