rs2235616

Positions:

• chr20-49952590-G-A
• chr20-49952590-G-C

Variant summary

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

The NM_018683.4(RNF114):​c.*449G>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 0.374 in 231,308 control chromosomes in the GnomAD database, including 18,340 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 (11076 hom., cov: 32)
  • Exomes 𝑓: 0.42 (7264 hom.)
• Consequence: RNF114 NM_018683.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF114	NM_018683.4	c.*449G>A		3_prime_UTR_variant	6/6	ENST00000244061.6	NP_061153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF114	ENST00000244061.6	c.*449G>A		3_prime_UTR_variant	6/6	1	NM_018683.4	ENSP00000244061.2
RNF114	ENST00000622920.1	c.*348G>A		3_prime_UTR_variant	5/5	5		ENSP00000485317.1
RNF114	ENST00000622999.3	n.*964G>A		non_coding_transcript_exon_variant	6/6	2		ENSP00000485203.1
RNF114	ENST00000622999.3	n.*964G>A		3_prime_UTR_variant	6/6	2		ENSP00000485203.1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53242 AN: 151960 Hom.: 11060 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.358

GnomAD4 exome AF: 0.420 AC: 33250 AN: 79230 Hom.: 7264 Cov.: 0 AF XY: 0.423 AC XY: 16982 AN XY: 40172

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.463

Gnomad4 ASJ exome AF: 0.332

Gnomad4 EAS exome AF: 0.356

Gnomad4 SAS exome AF: 0.592

Gnomad4 FIN exome AF: 0.575

Gnomad4 NFE exome AF: 0.428

Gnomad4 OTH exome AF: 0.402

GnomAD4 genome AF: 0.350 AC: 53292 AN: 152078 Hom.: 11076 Cov.: 32 AF XY: 0.364 AC XY: 27094 AN XY: 74358

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.563

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.359

Alfa AF: 0.399 Hom.: 12405

Bravo AF: 0.324

Asia WGS AF: 0.458 AC: 1594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.54
DANN	Benign	0.66

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: rs2235616; hg19: chr20-48569127; COSMIC: COSV54871445; COSMIC: COSV54871445;