20-49938440-C-G

Variant names:

• chr20-49938440-C-G
• rs2235617
• NM_018683.4:c.140+1888C>G

Variant summary

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

The NM_018683.4(RNF114):​c.140+1888C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 152,116 control chromosomes in the GnomAD database, including 11,058 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 (11058 hom., cov: 32)
• Consequence: RNF114 NM_018683.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.337
• Publications: 35 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=-0.84).
• 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.140+1888C>G		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.140+1888C>G		intron_variant	Intron 1 of 5	1	NM_018683.4	ENSP00000244061.2

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53232 AN: 151998 Hom.: 11042 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.350 AC: 53282 AN: 152116 Hom.: 11058 Cov.: 32 AF XY: 0.364 AC XY: 27076 AN XY: 74346

African (AFR) AF: 0.126 AC: 5223 AN: 41546

American (AMR) AF: 0.441 AC: 6736 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1136 AN: 3472

East Asian (EAS) AF: 0.344 AC: 1778 AN: 5170

South Asian (SAS) AF: 0.558 AC: 2690 AN: 4822

European-Finnish (FIN) AF: 0.563 AC: 5947 AN: 10566

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28637 AN: 67960

Other (OTH) AF: 0.358 AC: 756 AN: 2112

Alfa AF: 0.390 Hom.: 6686

Bravo AF: 0.324

Asia WGS AF: 0.458 AC: 1593 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.8
DANN	Benign	0.59
PhyloP100		-0.34
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: rs2235617; hg19: chr20-48554977;