chr11-71990477-G-A

Position:

• chr11-71990477-G-A

Variant summary

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

The NM_018320.5(RNF121):​c.507-120G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.958 in 1,289,150 control chromosomes in the GnomAD database, including 593,369 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 (65287 hom., cov: 33)
  • Exomes 𝑓: 0.96 (528082 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=-0.9).
• 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.507-120G>A		intron_variant		ENST00000361756.8	NP_060790.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF121	ENST00000361756.8	c.507-120G>A		intron_variant		1	NM_018320.5	ENSP00000354571	P1

Frequencies

GnomAD3 genomes AF: 0.924 AC: 140639 AN: 152178 Hom.: 65253 Cov.: 33

Gnomad AFR AF: 0.858

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.957

Gnomad EAS AF: 0.844

Gnomad SAS AF: 0.884

Gnomad FIN AF: 0.965

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.978

Gnomad OTH AF: 0.945

GnomAD4 exome AF: 0.963 AC: 1094804 AN: 1136854 Hom.: 528082 AF XY: 0.961 AC XY: 546592 AN XY: 568492

Gnomad4 AFR exome AF: 0.857

Gnomad4 AMR exome AF: 0.880

Gnomad4 ASJ exome AF: 0.959

Gnomad4 EAS exome AF: 0.840

Gnomad4 SAS exome AF: 0.893

Gnomad4 FIN exome AF: 0.968

Gnomad4 NFE exome AF: 0.980

Gnomad4 OTH exome AF: 0.954

GnomAD4 genome AF: 0.924 AC: 140730 AN: 152296 Hom.: 65287 Cov.: 33 AF XY: 0.920 AC XY: 68518 AN XY: 74482

Gnomad4 AFR AF: 0.858

Gnomad4 AMR AF: 0.857

Gnomad4 ASJ AF: 0.957

Gnomad4 EAS AF: 0.844

Gnomad4 SAS AF: 0.885

Gnomad4 FIN AF: 0.965

Gnomad4 NFE AF: 0.978

Gnomad4 OTH AF: 0.946

Alfa AF: 0.947 Hom.: 10776

Bravo AF: 0.917

Asia WGS AF: 0.878 AC: 3051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.67

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: rs2276384; hg19: chr11-71701523;