7-5622875-C-T

Variant names:

• chr7-5622875-C-T
• rs146694552
• NM_207111.4:c.2757G>A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2 BP4_Strong BP6_Very_Strong BP7 BS1

The NM_207111.4(RNF216):​c.2757G>A​(p.Pro919Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000587 in 1,602,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00059 (0 hom.)
• Consequence: RNF216 NM_207111.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -5.72

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 Benign. Variant got -15 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 7-5622875-C-T is Benign according to our data. Variant chr7-5622875-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 740477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-5622875-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-5.72 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000591 (90/152336) while in subpopulation AMR AF= 0.00183 (28/15306). AF 95% confidence interval is 0.0013. There are 0 homozygotes in gnomad4. There are 47 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF216	NM_207111.4	c.2757G>A	p.Pro919Pro	synonymous_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.2757G>A	p.Pro919Pro	synonymous_variant	Exon 17 of 17	1	NM_207111.4	ENSP00000374552.3
RNF216	ENST00000425013.6	c.2586G>A	p.Pro862Pro	synonymous_variant	Exon 17 of 17	1		ENSP00000404602.2
RNF216	ENST00000389900.8	n.*1874G>A		non_coding_transcript_exon_variant	Exon 16 of 16	1		ENSP00000374550.4
RNF216	ENST00000389900.8	n.*1874G>A		3_prime_UTR_variant	Exon 16 of 16	1		ENSP00000374550.4

Frequencies

GnomAD3 genomes AF: 0.000591 AC: 90 AN: 152218 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.000319 AC: 79 AN: 247410 Hom.: 0 AF XY: 0.000345 AC XY: 46 AN XY: 133500

Gnomad AFR exome AF: 0.000247

Gnomad AMR exome AF: 0.000727

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0000665

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000401

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.000587 AC: 851 AN: 1449774 Hom.: 0 Cov.: 31 AF XY: 0.000556 AC XY: 400 AN XY: 718786

Gnomad4 AFR exome AF: 0.000300

Gnomad4 AMR exome AF: 0.000653

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000508

Gnomad4 SAS exome AF: 0.0000233

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000710

Gnomad4 OTH exome AF: 0.000384

GnomAD4 genome AF: 0.000591 AC: 90 AN: 152336 Hom.: 0 Cov.: 32 AF XY: 0.000631 AC XY: 47 AN XY: 74494

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.00183

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000691

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.000345 Hom.: 0

Bravo AF: 0.000514

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

RNF216: BP4, BP7 -

Oct 15, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.026
DANN	Benign	0.76

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: rs146694552; hg19: chr7-5662506;