rs1056198

Variant names:

• chr20-49939692-C-T
• rs1056198
• NM_018683.4:c.141-1869C>T

Variant summary

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

The NM_018683.4(RNF114):​c.141-1869C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 151,342 control chromosomes in the GnomAD database, including 10,872 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 0.35 (10872 hom., cov: 30)
• Consequence: RNF114 NM_018683.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.357
• Publications: 31 publications found

Genes affected

RNF114 (HGNC:13094): (ring finger protein 114) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in protein polyubiquitination and ubiquitin-dependent protein catabolic process. Located in cytosol and plasma membrane. Biomarker of male infertility. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF114	NM_018683.4	c.141-1869C>T		intron_variant	Intron 1 of 5	ENST00000244061.6	NP_061153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF114	ENST00000244061.6	c.141-1869C>T		intron_variant	Intron 1 of 5	1	NM_018683.4	ENSP00000244061.2

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52769 AN: 151224 Hom.: 10856 Cov.: 30

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.349 AC: 52819 AN: 151342 Hom.: 10872 Cov.: 30 AF XY: 0.363 AC XY: 26808 AN XY: 73908

African (AFR) AF: 0.125 AC: 5189 AN: 41368

American (AMR) AF: 0.440 AC: 6665 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1128 AN: 3462

East Asian (EAS) AF: 0.342 AC: 1757 AN: 5142

South Asian (SAS) AF: 0.557 AC: 2678 AN: 4806

European-Finnish (FIN) AF: 0.560 AC: 5815 AN: 10376

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.420 AC: 28463 AN: 67736

Other (OTH) AF: 0.357 AC: 750 AN: 2098

Alfa AF: 0.410 Hom.: 6991

Bravo AF: 0.324

Asia WGS AF: 0.458 AC: 1592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.59
PhyloP100		-0.36
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: rs1056198; hg19: chr20-48556229; COSMIC: COSV54868948; COSMIC: COSV54868948;