rs2276384

Variant names:

• chr11-71990477-G-A
• rs2276384
• NM_018320.5:c.507-120G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RNF121	NM_018320.5	c.507-120G>A		intron_variant	Intron 5 of 8	ENST00000361756.8	NP_060790.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF121	ENST00000361756.8	c.507-120G>A		intron_variant	Intron 5 of 8	1	NM_018320.5	ENSP00000354571.3

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

African (AFR) AF: 0.857 AC: 21968 AN: 25632

American (AMR) AF: 0.880 AC: 25384 AN: 28842

Ashkenazi Jewish (ASJ) AF: 0.959 AC: 17879 AN: 18646

East Asian (EAS) AF: 0.840 AC: 31749 AN: 37794

South Asian (SAS) AF: 0.893 AC: 58041 AN: 65016

European-Finnish (FIN) AF: 0.968 AC: 40611 AN: 41946

Middle Eastern (MID) AF: 0.967 AC: 4020 AN: 4156

European-Non Finnish (NFE) AF: 0.980 AC: 848362 AN: 865786

Other (OTH) AF: 0.954 AC: 46790 AN: 49036

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

African (AFR) AF: 0.858 AC: 35634 AN: 41540

American (AMR) AF: 0.857 AC: 13119 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.957 AC: 3323 AN: 3472

East Asian (EAS) AF: 0.844 AC: 4374 AN: 5184

South Asian (SAS) AF: 0.885 AC: 4267 AN: 4824

European-Finnish (FIN) AF: 0.965 AC: 10245 AN: 10618

Middle Eastern (MID) AF: 0.969 AC: 285 AN: 294

European-Non Finnish (NFE) AF: 0.978 AC: 66573 AN: 68038

Other (OTH) AF: 0.946 AC: 1998 AN: 2112

Alfa AF: 0.944 Hom.: 11070

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
PhyloP100		-0.17
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: rs2276384; hg19: chr11-71701523;