20-49952392-G-T

Position:

• chr20-49952392-G-T

Variant summary

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

The NM_018683.4(RNF114):​c.*251G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 539,326 control chromosomes in the GnomAD database, including 47,035 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 (11068 hom., cov: 32)
  • Exomes 𝑓: 0.42 (35967 hom.)
• Consequence: RNF114 NM_018683.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.374

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.*251G>T		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.*251G>T		3_prime_UTR_variant	6/6	1	NM_018683.4	ENSP00000244061.2
RNF114	ENST00000622920.1	c.*150G>T		3_prime_UTR_variant	5/5	5		ENSP00000485317.1
RNF114	ENST00000622999.3	n.*766G>T		non_coding_transcript_exon_variant	6/6	2		ENSP00000485203.1
RNF114	ENST00000622999.3	n.*766G>T		3_prime_UTR_variant	6/6	2		ENSP00000485203.1

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53218 AN: 151820 Hom.: 11052 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.358

GnomAD4 exome AF: 0.421 AC: 163221 AN: 387388 Hom.: 35967 Cov.: 0 AF XY: 0.428 AC XY: 86640 AN XY: 202274

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.456

Gnomad4 ASJ exome AF: 0.317

Gnomad4 EAS exome AF: 0.339

Gnomad4 SAS exome AF: 0.561

Gnomad4 FIN exome AF: 0.558

Gnomad4 NFE exome AF: 0.418

Gnomad4 OTH exome AF: 0.391

GnomAD4 genome AF: 0.351 AC: 53268 AN: 151938 Hom.: 11068 Cov.: 32 AF XY: 0.365 AC XY: 27065 AN XY: 74238

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.359

Alfa AF: 0.380 Hom.: 10723

Bravo AF: 0.324

Asia WGS AF: 0.459 AC: 1597 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	2.8
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6125829; hg19: chr20-48568929; COSMIC: COSV54871437; COSMIC: COSV54871437;