7-5622917-C-A

Variant names:

• chr7-5622917-C-A
• rs148282284
• NM_207111.4:c.2715G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_207111.4(RNF216):​c.2715G>T​(p.Met905Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,460,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: RNF216 NM_207111.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036733896).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF216	NM_207111.4	c.2715G>T	p.Met905Ile	missense_variant	Exon 17 of 17	ENST00000389902.8	NP_996994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF216	ENST00000389902.8	c.2715G>T	p.Met905Ile	missense_variant	Exon 17 of 17	1	NM_207111.4	ENSP00000374552.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000797 AC: 2 AN: 250790 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135468

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000110 AC: 16 AN: 1460864 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726554

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	10
DANN	Benign	0.95
DEOGEN2	Benign	0.034	T;.
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.037	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.20	N;N
REVEL	Benign	0.041
Sift	Benign	0.25	T;T
Sift4G	Benign	0.48	T;T
Polyphen		0.0	B;B
Vest4		0.076
MutPred		0.22		Loss of disorder (P = 0.0377);.;
MVP		0.20
MPC		0.028
ClinPred		0.019	T
GERP RS		2.0
Varity_R		0.035
gMVP		0.11

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: rs148282284; hg19: chr7-5662548;