17-80353526-C-T

Variant names:

• chr17-80353526-C-T
• rs148139681
• NM_001256071.3:c.10438C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS1

The NM_001256071.3(RNF213):​c.10438C>T​(p.Arg3480Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000235 in 1,610,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: RNF213 NM_001256071.3 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.48
• Publications: 1 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.032948315).
• BP6: Variant 17-80353526-C-T is Benign according to our data. Variant chr17-80353526-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 808332.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000302 (46/152132) while in subpopulation AMR AF = 0.00111 (17/15276). AF 95% confidence interval is 0.000708. There are 0 homozygotes in GnomAd4. There are 22 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256071.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF213	NM_001256071.3	MANE Select	c.10438C>T	p.Arg3480Trp	missense	Exon 34 of 68	NP_001243000.2	A0A0A0MTR7
	RNF213	NM_001410195.1		c.10585C>T	p.Arg3529Trp	missense	Exon 35 of 69	NP_001397124.1	A0A0A0MTC1
	RNF213	NM_020914.5		c.10585C>T	p.Arg3529Trp	missense	Exon 35 of 69	NP_065965.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF213	ENST00000582970.6	TSL:1 MANE Select	c.10438C>T	p.Arg3480Trp	missense	Exon 34 of 68	ENSP00000464087.1	A0A0A0MTR7
	RNF213	ENST00000508628.6	TSL:5	c.10585C>T	p.Arg3529Trp	missense	Exon 35 of 69	ENSP00000425956.2	A0A0A0MTC1
	RNF213-AS1	ENST00000575034.5	TSL:2	n.1953G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.000302 AC: 46 AN: 152132 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000227 AC: 55 AN: 242804 AF XY: 0.000236

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000505

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000189

Gnomad NFE exome AF: 0.000304

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.000228 AC: 332 AN: 1458834 Hom.: 0 Cov.: 30 AF XY: 0.000230 AC XY: 167 AN XY: 725342

African (AFR) AF: 0.000179 AC: 6 AN: 33458

American (AMR) AF: 0.000658 AC: 29 AN: 44084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39612

South Asian (SAS) AF: 0.00 AC: 0 AN: 85794

European-Finnish (FIN) AF: 0.000188 AC: 10 AN: 53192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000251 AC: 279 AN: 1110526

Other (OTH) AF: 0.000133 AC: 8 AN: 60320

GnomAD4 genome AF: 0.000302 AC: 46 AN: 152132 Hom.: 0 Cov.: 33 AF XY: 0.000296 AC XY: 22 AN XY: 74308

African (AFR) AF: 0.0000241 AC: 1 AN: 41414

American (AMR) AF: 0.00111 AC: 17 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000367 AC: 25 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000257 Hom.: 0

Bravo AF: 0.000351

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000173 AC: 21

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.11
DANN	Benign	0.71
DEOGEN2	Benign	0.011	T
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.5
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-1.1	T
PhyloP100		-4.5
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.014
Sift	Benign	0.057	T
Sift4G	Benign	0.12	T
Vest4		0.086
MVP		0.099
MPC		0.34
ClinPred		0.039	T
GERP RS		-5.7
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.1
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs148139681; hg19: chr17-78327326;