7-5623040-G-A

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

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.27
Variant links:
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]

Genome browser will be placed here

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
RNF216NM_207111.4 linkuse as main transcriptc.2592C>T p.Phe864= synonymous_variant 17/17 ENST00000389902.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNF216ENST00000389902.8 linkuse as main transcriptc.2592C>T p.Phe864= synonymous_variant 17/171 NM_207111.4 P4Q9NWF9-1
RNF216ENST00000425013.6 linkuse as main transcriptc.2421C>T p.Phe807= synonymous_variant 17/171 A1Q9NWF9-2
RNF216ENST00000389900.8 linkuse as main transcriptc.*1709C>T 3_prime_UTR_variant, NMD_transcript_variant 16/161
RNF216ENST00000469375.1 linkuse as main transcriptn.809C>T non_coding_transcript_exon_variant 4/43

Frequencies

GnomAD3 genomes
AF:
0.000664
AC:
101
AN:
152188
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0185
Gnomad SAS
AF:
0.000827
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00167
AC:
417
AN:
250412
Hom.:
5
AF XY:
0.00159
AC XY:
215
AN XY:
135456
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0216
Gnomad SAS exome
AF:
0.000523
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000492
AC:
719
AN:
1461768
Hom.:
7
Cov.:
31
AF XY:
0.000499
AC XY:
363
AN XY:
727182
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0157
Gnomad4 SAS exome
AF:
0.000649
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000719
Gnomad4 OTH exome
AF:
0.000480
GnomAD4 genome
AF:
0.000670
AC:
102
AN:
152306
Hom.:
1
Cov.:
32
AF XY:
0.000899
AC XY:
67
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0187
Gnomad4 SAS
AF:
0.000828
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000693
Hom.:
0
Bravo
AF:
0.00103
Asia WGS
AF:
0.00520
AC:
18
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 submitterclinical testingInvitaeDec 19, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
CADD
Benign
6.9
DANN
Benign
0.64

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs150494013; hg19: chr7-5662671; COSMIC: COSV66289523; API