17-80353531-G-A

Position:

• chr17-80353531-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001256071.3(RNF213):​c.10443G>A​(p.Ala3481Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,611,970 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0068 (21 hom., cov: 33)
  • Exomes 𝑓: 0.00070 (8 hom.)
• Consequence: RNF213 NM_001256071.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.47

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:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 17-80353531-G-A is Benign according to our data. Variant chr17-80353531-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 777225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.47 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00683 (1040/152284) while in subpopulation AFR AF= 0.0235 (976/41552). AF 95% confidence interval is 0.0223. There are 21 homozygotes in gnomad4. There are 522 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 21 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF213	NM_001256071.3	c.10443G>A	p.Ala3481Ala	synonymous_variant	34/68	ENST00000582970.6	NP_001243000.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF213	ENST00000582970.6	c.10443G>A	p.Ala3481Ala	synonymous_variant	34/68	1	NM_001256071.3	ENSP00000464087.1
RNF213	ENST00000508628.6	c.10590G>A	p.Ala3530Ala	synonymous_variant	35/69	5		ENSP00000425956.2
RNF213-AS1	ENST00000575034.5	n.1948C>T		non_coding_transcript_exon_variant	2/2	2
RNF213-AS1	ENST00000613190.1	n.281C>T		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes AF: 0.00683 AC: 1040 AN: 152166 Hom.: 21 Cov.: 33

Gnomad AFR AF: 0.0235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00167 AC: 410 AN: 244866 Hom.: 2 AF XY: 0.00133 AC XY: 176 AN XY: 132512

Gnomad AFR exome AF: 0.0202

Gnomad AMR exome AF: 0.00180

Gnomad ASJ exome AF: 0.000500

Gnomad EAS exome AF: 0.0000555

Gnomad SAS exome AF: 0.0000662

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000146

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.000702 AC: 1025 AN: 1459686 Hom.: 8 Cov.: 30 AF XY: 0.000584 AC XY: 424 AN XY: 725896

Gnomad4 AFR exome AF: 0.0217

Gnomad4 AMR exome AF: 0.00215

Gnomad4 ASJ exome AF: 0.000306

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000720

Gnomad4 OTH exome AF: 0.00159

GnomAD4 genome AF: 0.00683 AC: 1040 AN: 152284 Hom.: 21 Cov.: 33 AF XY: 0.00701 AC XY: 522 AN XY: 74450

Gnomad4 AFR AF: 0.0235

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00412 Hom.: 3

Bravo AF: 0.00762

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 22, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Moyamoya disease 2 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Nov 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.99
DANN	Benign	0.69
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.1

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

Other links and lift over

dbSNP: rs116677277; hg19: chr17-78327331;