rs1044673

Positions:

• chr15-59097267-G-A
• chr15-59097267-G-T

Variant summary

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

The NM_017610.8(RNF111):​c.*2367G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0694 in 152,242 control chromosomes in the GnomAD database, including 359 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 0.069 (359 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: RNF111 NM_017610.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.082 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF111	NM_017610.8	c.*2367G>A		3_prime_UTR_variant	14/14	ENST00000348370.9	NP_060080.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF111	ENST00000348370.9	c.*2367G>A		3_prime_UTR_variant	14/14	1	NM_017610.8	ENSP00000288199.5

Frequencies

GnomAD3 genomes AF: 0.0693 AC: 10544 AN: 152124 Hom.: 356 Cov.: 33

Gnomad AFR AF: 0.0842

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.0783

Gnomad ASJ AF: 0.0640

Gnomad EAS AF: 0.0294

Gnomad SAS AF: 0.0782

Gnomad FIN AF: 0.0867

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0581

Gnomad OTH AF: 0.0598

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0694 AC: 10562 AN: 152242 Hom.: 359 Cov.: 33 AF XY: 0.0702 AC XY: 5225 AN XY: 74420

Gnomad4 AFR AF: 0.0843

Gnomad4 AMR AF: 0.0789

Gnomad4 ASJ AF: 0.0640

Gnomad4 EAS AF: 0.0295

Gnomad4 SAS AF: 0.0774

Gnomad4 FIN AF: 0.0867

Gnomad4 NFE AF: 0.0581

Gnomad4 OTH AF: 0.0591

Alfa AF: 0.0364 Hom.: 32

Bravo AF: 0.0709

Asia WGS AF: 0.0500 AC: 173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.9
DANN	Benign	0.40

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: rs1044673; hg19: chr15-59389466;