17-58355001-C-G

Variant names:

• chr17-58355001-C-G
• rs2158460
• NM_017763.6:c.2309-15G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017763.6(RNF43):​c.2309-15G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,609,502 control chromosomes in the GnomAD database, including 23,599 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2215 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21384 hom.)
• Consequence: RNF43 NM_017763.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.771
• Publications: 14 publications found

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]

ENSG00000285897 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 17-58355001-C-G is Benign according to our data. Variant chr17-58355001-C-G is described in ClinVar as Benign. ClinVar VariationId is 403383.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017763.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF43	NM_017763.6	MANE Select	c.2309-15G>C		intron	N/A	NP_060233.3
	RNF43	NM_001305544.3		c.2309-15G>C		intron	N/A	NP_001292473.1
	RNF43	NM_001438822.1		c.2309-15G>C		intron	N/A	NP_001425751.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF43	ENST00000407977.7	TSL:2 MANE Select	c.2309-15G>C		intron	N/A	ENSP00000385328.2
	RNF43	ENST00000577716.5	TSL:1	c.2309-15G>C		intron	N/A	ENSP00000462764.1
	RNF43	ENST00000584437.5	TSL:1	c.2309-15G>C		intron	N/A	ENSP00000463069.1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25723 AN: 151898 Hom.: 2207 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.0775

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.160

GnomAD2 exomes AF: 0.163 AC: 40716 AN: 249950 AF XY: 0.159

Gnomad AFR exome AF: 0.151

Gnomad AMR exome AF: 0.168

Gnomad ASJ exome AF: 0.0812

Gnomad EAS exome AF: 0.193

Gnomad FIN exome AF: 0.212

Gnomad NFE exome AF: 0.169

Gnomad OTH exome AF: 0.146

GnomAD4 exome AF: 0.168 AC: 244159 AN: 1457486 Hom.: 21384 Cov.: 31 AF XY: 0.165 AC XY: 120011 AN XY: 725172

African (AFR) AF: 0.150 AC: 4985 AN: 33320

American (AMR) AF: 0.171 AC: 7651 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.0816 AC: 2130 AN: 26118

East Asian (EAS) AF: 0.215 AC: 8537 AN: 39676

South Asian (SAS) AF: 0.121 AC: 10436 AN: 86144

European-Finnish (FIN) AF: 0.209 AC: 11126 AN: 53354

Middle Eastern (MID) AF: 0.0761 AC: 428 AN: 5622

European-Non Finnish (NFE) AF: 0.171 AC: 189670 AN: 1108334

Other (OTH) AF: 0.153 AC: 9196 AN: 60254

GnomAD4 genome AF: 0.169 AC: 25764 AN: 152016 Hom.: 2215 Cov.: 32 AF XY: 0.171 AC XY: 12704 AN XY: 74286

African (AFR) AF: 0.155 AC: 6431 AN: 41448

American (AMR) AF: 0.189 AC: 2885 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0775 AC: 269 AN: 3472

East Asian (EAS) AF: 0.199 AC: 1031 AN: 5172

South Asian (SAS) AF: 0.116 AC: 557 AN: 4818

European-Finnish (FIN) AF: 0.216 AC: 2279 AN: 10552

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11739 AN: 67966

Other (OTH) AF: 0.157 AC: 331 AN: 2108

Alfa AF: 0.104 Hom.: 221

Bravo AF: 0.164

Asia WGS AF: 0.152 AC: 529 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	not provided (3)
-	-	1	Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.72
PhyloP100		0.77
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2158460; hg19: chr17-56432362; COSMIC: COSV56642823; COSMIC: COSV56642823;