rs1056198

chr20-49939692-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
RNF114	NM_018683.4	c.141-1869C>T		intron_variant		ENST00000244061.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF114	ENST00000244061.6	c.141-1869C>T		intron_variant		1	NM_018683.4	P1

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

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.342

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.560

Gnomad4 NFE AF: 0.420

Gnomad4 OTH AF: 0.357

Alfa AF: 0.413 Hom.: 6324

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

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: rs1056198; hg19: chr20-48556229; COSMIC: COSV54868948; COSMIC: COSV54868948;