rs1468996

Variant names:

• chr7-5694826-C-T
• rs1468996
• NM_207111.4:c.2061+16935G>A

Variant summary

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

The NM_207111.4(RNF216):​c.2061+16935G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 152,058 control chromosomes in the GnomAD database, including 11,426 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 0.36 (11426 hom., cov: 32)
• Consequence: RNF216 NM_207111.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210
• Publications: 4 publications found

Genes affected

RNF216 (HGNC:21698): (ring finger protein 216) This gene encodes a cytoplasmic protein which specifically colocalizes and interacts with the serine/threonine protein kinase, receptor-interacting protein (RIP). Zinc finger domains of the encoded protein are required for its interaction with RIP and for inhibition of TNF- and IL1-induced NF-kappa B activation pathways. The encoded protein may also function as an E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes and transfers it to substrates. Several alternatively spliced transcript variants have been described for this locus but the full-length natures of only some are known. [provided by RefSeq, Jul 2008]

RNF216 Gene-Disease associations (from GenCC):

• cerebellar ataxia-hypogonadism syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000309716 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF216	NM_207111.4	c.2061+16935G>A		intron_variant	Intron 13 of 16	ENST00000389902.8	NP_996994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF216	ENST00000389902.8	c.2061+16935G>A		intron_variant	Intron 13 of 16	1	NM_207111.4	ENSP00000374552.3

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54943 AN: 151940 Hom.: 11427 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.399

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.361 AC: 54939 AN: 152058 Hom.: 11426 Cov.: 32 AF XY: 0.363 AC XY: 27000 AN XY: 74318

African (AFR) AF: 0.167 AC: 6917 AN: 41488

American (AMR) AF: 0.342 AC: 5223 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1874 AN: 3472

East Asian (EAS) AF: 0.758 AC: 3921 AN: 5174

South Asian (SAS) AF: 0.417 AC: 2007 AN: 4816

European-Finnish (FIN) AF: 0.450 AC: 4737 AN: 10536

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28838 AN: 67976

Other (OTH) AF: 0.400 AC: 843 AN: 2106

Alfa AF: 0.414 Hom.: 8976

Bravo AF: 0.348

Asia WGS AF: 0.506 AC: 1759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.6
DANN	Benign	0.32
PhyloP100		0.021
Mutation Taster		=100/0	polymorphism (auto)

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: rs1468996; hg19: chr7-5734457;