17-58354727-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_017763.6(RNF43):c.*216C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 590,738 control chromosomes in the GnomAD database, including 178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (30 hom., cov: 33)
  • Exomes 𝑓: 0.019 (148 hom.)
• Consequence: RNF43 NM_017763.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.492

Genes affected

RNF43 (HGNC:18505): (ring finger protein 43) The protein encoded by this gene is a RING-type E3 ubiquitin ligase and is predicted to contain a transmembrane domain, a protease-associated domain, an ectodomain, and a cytoplasmic RING domain. This protein is thought to negatively regulate Wnt signaling, and expression of this gene results in an increase in ubiquitination of frizzled receptors, an alteration in their subcellular distribution, resulting in reduced surface levels of these receptors. Mutations in this gene have been reported in multiple tumor cells, including colorectal and endometrial cancers. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2015]

TSPOAP1-AS1 (HGNC:44148): (TSPOAP1, SUPT4H1 and RNF43 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 17-58354727-G-A is Benign according to our data. Variant chr17-58354727-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1317600.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF43	NM_017763.6	c.*216C>T		3_prime_UTR_variant	10/10	ENST00000407977.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF43	ENST00000407977.7	c.*216C>T		3_prime_UTR_variant	10/10	2	NM_017763.6	P1
TSPOAP1-AS1	ENST00000583841.1	n.434+17048G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0179 AC: 2721 AN: 152230 Hom.: 30 Cov.: 33

Gnomad AFR AF: 0.0205

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0153

Gnomad ASJ AF: 0.0450

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0327

Gnomad FIN AF: 0.0247

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0147

Gnomad OTH AF: 0.0229

GnomAD4 exome AF: 0.0192 AC: 8404 AN: 438390 Hom.: 148 Cov.: 4 AF XY: 0.0205 AC XY: 4748 AN XY: 231116

Gnomad4 AFR exome AF: 0.0217

Gnomad4 AMR exome AF: 0.0123

Gnomad4 ASJ exome AF: 0.0464

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0386

Gnomad4 FIN exome AF: 0.0249

Gnomad4 NFE exome AF: 0.0156

Gnomad4 OTH exome AF: 0.0213

GnomAD4 genome AF: 0.0178 AC: 2719 AN: 152348 Hom.: 30 Cov.: 33 AF XY: 0.0185 AC XY: 1378 AN XY: 74502

Gnomad4 AFR AF: 0.0204

Gnomad4 AMR AF: 0.0153

Gnomad4 ASJ AF: 0.0450

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0329

Gnomad4 FIN AF: 0.0247

Gnomad4 NFE AF: 0.0147

Gnomad4 OTH AF: 0.0222

Alfa AF: 0.0162 Hom.: 11

Bravo AF: 0.0172

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 15, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	6.0
Dann	Benign	0.86

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: rs115803058; hg19: chr17-56432088;