20-49938133-A-G

Variant names:

• chr20-49938133-A-G
• rs2038127
• NM_018683.4:c.140+1581A>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+1581A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,136 control chromosomes in the GnomAD database, including 4,545 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 0.24 (4545 hom., cov: 32)
• Consequence: RNF114 NM_018683.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 12 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018683.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF114	NM_018683.4	MANE Select	c.140+1581A>G		intron	N/A	NP_061153.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF114	ENST00000244061.6	TSL:1 MANE Select	c.140+1581A>G		intron	N/A	ENSP00000244061.2
	RNF114	ENST00000917362.1		c.140+1581A>G		intron	N/A	ENSP00000587421.1
	RNF114	ENST00000953155.1		c.140+1581A>G		intron	N/A	ENSP00000623214.1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36096 AN: 152018 Hom.: 4547 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.0681

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.237 AC: 36093 AN: 152136 Hom.: 4545 Cov.: 32 AF XY: 0.230 AC XY: 17070 AN XY: 74364

African (AFR) AF: 0.184 AC: 7632 AN: 41512

American (AMR) AF: 0.211 AC: 3221 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 952 AN: 3470

East Asian (EAS) AF: 0.0679 AC: 352 AN: 5184

South Asian (SAS) AF: 0.161 AC: 780 AN: 4830

European-Finnish (FIN) AF: 0.215 AC: 2272 AN: 10580

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19946 AN: 67986

Other (OTH) AF: 0.245 AC: 518 AN: 2110

Alfa AF: 0.272 Hom.: 18839

Bravo AF: 0.237

Asia WGS AF: 0.119 AC: 417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.51
DANN	Benign	0.52
PhyloP100		-2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2038127; hg19: chr20-48554670;