rs10515155

Variant names:

• chr17-58404583-A-G
• rs10515155
• NM_017763.6:c.252+10743T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017763.6(RNF43):​c.252+10743T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,124 control chromosomes in the GnomAD database, including 2,729 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (2729 hom., cov: 32)
• Consequence: RNF43 NM_017763.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF43	NM_017763.6	c.252+10743T>C		intron_variant	Intron 2 of 9	ENST00000407977.7	NP_060233.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF43	ENST00000407977.7	c.252+10743T>C		intron_variant	Intron 2 of 9	2	NM_017763.6	ENSP00000385328.2
ENSG00000285897	ENST00000648873.1	n.252+10743T>C		intron_variant	Intron 1 of 12			ENSP00000497686.1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28237 AN: 152006 Hom.: 2727 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.0829

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.174

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.186 AC: 28251 AN: 152124 Hom.: 2729 Cov.: 32 AF XY: 0.187 AC XY: 13922 AN XY: 74364

African (AFR) AF: 0.153 AC: 6366 AN: 41486

American (AMR) AF: 0.203 AC: 3097 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0829 AC: 287 AN: 3464

East Asian (EAS) AF: 0.171 AC: 887 AN: 5180

South Asian (SAS) AF: 0.124 AC: 597 AN: 4820

European-Finnish (FIN) AF: 0.240 AC: 2543 AN: 10582

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13813 AN: 67986

Other (OTH) AF: 0.171 AC: 362 AN: 2114

Alfa AF: 0.186 Hom.: 1228

Bravo AF: 0.177

Asia WGS AF: 0.157 AC: 546 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.0
DANN	Benign	0.54
PhyloP100		0.0
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: rs10515155; hg19: chr17-56481944; COSMIC: COSV107515316; COSMIC: COSV107515316;