15-59055159-G-A

Position:

• chr15-59055159-G-A

Variant summary

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

The NM_017610.8(RNF111):​c.1008-523G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 151,900 control chromosomes in the GnomAD database, including 13,062 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 0.41 (13062 hom., cov: 32)
• Consequence: RNF111 NM_017610.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF111	NM_017610.8	c.1008-523G>A		intron_variant		ENST00000348370.9	NP_060080.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF111	ENST00000348370.9	c.1008-523G>A		intron_variant		1	NM_017610.8	ENSP00000288199	A1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61687 AN: 151782 Hom.: 13041 Cov.: 32

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.407 AC: 61753 AN: 151900 Hom.: 13062 Cov.: 32 AF XY: 0.406 AC XY: 30143 AN XY: 74256

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.355

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.402

Alfa AF: 0.386 Hom.: 3548

Bravo AF: 0.424

Asia WGS AF: 0.398 AC: 1381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.43
DANN	Benign	0.31

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: rs10431791; hg19: chr15-59347358;