7-5623040-G-A
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_207111.4(RNF216):c.2592C>T(p.Phe864=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000509 in 1,614,074 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00067 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00049 ( 7 hom. )
Consequence
RNF216
NM_207111.4 synonymous
NM_207111.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.27
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
Variant 7-5623040-G-A is Benign according to our data. Variant chr7-5623040-G-A is described in ClinVar as [Benign]. Clinvar id is 1598947.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-5623040-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=1.27 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00067 (102/152306) while in subpopulation EAS AF= 0.0187 (97/5176). AF 95% confidence interval is 0.0157. There are 1 homozygotes in gnomad4. There are 67 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 7 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RNF216 | NM_207111.4 | c.2592C>T | p.Phe864= | synonymous_variant | 17/17 | ENST00000389902.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RNF216 | ENST00000389902.8 | c.2592C>T | p.Phe864= | synonymous_variant | 17/17 | 1 | NM_207111.4 | P4 | |
RNF216 | ENST00000425013.6 | c.2421C>T | p.Phe807= | synonymous_variant | 17/17 | 1 | A1 | ||
RNF216 | ENST00000389900.8 | c.*1709C>T | 3_prime_UTR_variant, NMD_transcript_variant | 16/16 | 1 | ||||
RNF216 | ENST00000469375.1 | n.809C>T | non_coding_transcript_exon_variant | 4/4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.000664 AC: 101AN: 152188Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00167 AC: 417AN: 250412Hom.: 5 AF XY: 0.00159 AC XY: 215AN XY: 135456
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GnomAD4 exome AF: 0.000492 AC: 719AN: 1461768Hom.: 7 Cov.: 31 AF XY: 0.000499 AC XY: 363AN XY: 727182
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GnomAD4 genome AF: 0.000670 AC: 102AN: 152306Hom.: 1 Cov.: 32 AF XY: 0.000899 AC XY: 67AN XY: 74488
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 19, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at