NM_017610.8:c.2424-412C>T

Variant names:

• chr15-59085247-C-T
• rs10518996
• NM_017610.8:c.2424-412C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017610.8(RNF111):​c.2424-412C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 151,956 control chromosomes in the GnomAD database, including 13,848 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 0.40 (13848 hom., cov: 32)
• Consequence: RNF111 NM_017610.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.797

Genes affected

RNF111 (HGNC:17384): (ring finger protein 111) The protein encoded by this gene is a nuclear RING-domain containing E3 ubiquitin ligase. This protein interacts with the transforming growth factor (TGF) -beta/NODAL signaling pathway by promoting the ubiquitination and proteosomal degradation of negative regulators, like SMAD proteins, and thereby enhances TGF-beta target-gene transcription. As a modulator of the nodal signaling cascade, this gene plays a critical role in the induction of mesoderm during embryonic development. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF111	NM_017610.8	c.2424-412C>T		intron_variant	Intron 9 of 13	ENST00000348370.9	NP_060080.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF111	ENST00000348370.9	c.2424-412C>T		intron_variant	Intron 9 of 13	1	NM_017610.8	ENSP00000288199.5

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60186 AN: 151838 Hom.: 13811 Cov.: 32

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.397 AC: 60273 AN: 151956 Hom.: 13848 Cov.: 32 AF XY: 0.396 AC XY: 29383 AN XY: 74250

Gnomad4 AFR AF: 0.635

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.392

Alfa AF: 0.295 Hom.: 13940

Bravo AF: 0.422

Asia WGS AF: 0.399 AC: 1385 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.7
DANN	Benign	0.52

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: rs10518996; hg19: chr15-59377446;