rs4945392

Positions:

• chr11-71983599-C-T

Variant summary

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

The NM_018320.5(RNF121):​c.398+684C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.92 in 152,298 control chromosomes in the GnomAD database, including 64,825 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 0.92 (64821 hom., cov: 34)
  • Exomes 𝑓: 1.0 (4 hom.)
• Consequence: RNF121 NM_018320.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165

Genes affected

RNF121 (HGNC:21070): (ring finger protein 121) The protein encoded by this gene contains a RING finger, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. Several alternatively spliced transcript variants have been noted for this gene, however, not all are likely to encode viable protein products. [provided by RefSeq, Sep 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF121	NM_018320.5	c.398+684C>T		intron_variant		ENST00000361756.8	NP_060790.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF121	ENST00000361756.8	c.398+684C>T		intron_variant		1	NM_018320.5	ENSP00000354571	P1

Frequencies

GnomAD3 genomes AF: 0.921 AC: 140090 AN: 152172 Hom.: 64788 Cov.: 34

Gnomad AFR AF: 0.845

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.957

Gnomad EAS AF: 0.844

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.965

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.979

Gnomad OTH AF: 0.941

GnomAD4 exome AF: 1.00 AC: 8 AN: 8 Hom.: 4 AF XY: 1.00 AC XY: 4 AN XY: 4

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.920 AC: 140180 AN: 152290 Hom.: 64821 Cov.: 34 AF XY: 0.916 AC XY: 68224 AN XY: 74458

Gnomad4 AFR AF: 0.845

Gnomad4 AMR AF: 0.857

Gnomad4 ASJ AF: 0.957

Gnomad4 EAS AF: 0.843

Gnomad4 SAS AF: 0.886

Gnomad4 FIN AF: 0.965

Gnomad4 NFE AF: 0.979

Gnomad4 OTH AF: 0.942

Alfa AF: 0.949 Hom.: 10000

Bravo AF: 0.913

Asia WGS AF: 0.876 AC: 3046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	17
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs4945392; hg19: chr11-71694645;