NM_018320.5:c.398+684C>T

Variant names:

• chr11-71983599-C-T
• rs4945392
• NM_018320.5:c.398+684C>T

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018320.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF121	NM_018320.5	MANE Select	c.398+684C>T		intron	N/A	NP_060790.2
	RNF121	NM_001300926.2		c.302+684C>T		intron	N/A	NP_001287855.1
	RNF121	NR_024147.2		n.376+684C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF121	ENST00000361756.8	TSL:1 MANE Select	c.398+684C>T		intron	N/A	ENSP00000354571.3
	RNF121	ENST00000530137.1	TSL:1	c.302+684C>T		intron	N/A	ENSP00000431286.1
	RNF121	ENST00000393713.7	TSL:1	c.302+684C>T		intron	N/A	ENSP00000377316.3

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 8 AN: 8

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.845 AC: 35098 AN: 41536

American (AMR) AF: 0.857 AC: 13096 AN: 15290

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

East Asian (EAS) AF: 0.843 AC: 4373 AN: 5186

South Asian (SAS) AF: 0.886 AC: 4272 AN: 4824

European-Finnish (FIN) AF: 0.965 AC: 10242 AN: 10614

Middle Eastern (MID) AF: 0.973 AC: 286 AN: 294

European-Non Finnish (NFE) AF: 0.979 AC: 66586 AN: 68048

Other (OTH) AF: 0.942 AC: 1992 AN: 2114

Alfa AF: 0.946 Hom.: 10292

Bravo AF: 0.913

Asia WGS AF: 0.876 AC: 3046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	17
DANN	Benign	0.69
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4945392; hg19: chr11-71694645;