rs1693534

chr15-58989763-T-G

Variant summary

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

The NM_017610.8(RNF111):c.-20+1695T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 152,090 control chromosomes in the GnomAD database, including 34,877 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 0.66 (34877 hom., cov: 32)
• Consequence: RNF111 NM_017610.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.682

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF111	NM_017610.8	c.-20+1695T>G		intron_variant		ENST00000348370.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF111	ENST00000348370.9	c.-20+1695T>G		intron_variant		1	NM_017610.8	A1

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100192 AN: 151972 Hom.: 34871 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.850

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.671

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

GnomAD4 genome AF: 0.659 AC: 100241 AN: 152090 Hom.: 34877 Cov.: 32 AF XY: 0.663 AC XY: 49310 AN XY: 74362

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.582

Gnomad4 SAS AF: 0.849

Gnomad4 FIN AF: 0.745

Gnomad4 NFE AF: 0.770

Gnomad4 OTH AF: 0.671

Alfa AF: 0.752 Hom.: 21753

Bravo AF: 0.640

Asia WGS AF: 0.666 AC: 2315 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	5.6
Dann	Benign	0.67

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: rs1693534; hg19: chr15-59281962;