rs3896232

chr1-44544129-A-G

Variant summary

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

The NM_018150.4(RNF220):c.626-70036A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,142 control chromosomes in the GnomAD database, including 5,460 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 0.26 (5460 hom., cov: 32)
• Consequence: RNF220 NM_018150.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.285

Genes affected

RNF220 (HGNC:25552): (ring finger protein 220) Predicted to enable ubiquitin protein ligase activity. Involved in positive regulation of canonical Wnt signaling pathway. Part of protein-containing complex. [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 (AFR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF220	NM_018150.4	c.626-70036A>G		intron_variant		ENST00000361799.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF220	ENST00000361799.7	c.626-70036A>G		intron_variant		1	NM_018150.4	P1
RNF220	ENST00000355387.6	c.626-70036A>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39698 AN: 152024 Hom.: 5463 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.252

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.261 AC: 39704 AN: 152142 Hom.: 5460 Cov.: 32 AF XY: 0.260 AC XY: 19315 AN XY: 74380

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.252

Alfa AF: 0.240 Hom.: 4498

Bravo AF: 0.262

Asia WGS AF: 0.212 AC: 739 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	5.1
Dann	Benign	0.63

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: rs3896232; hg19: chr1-45009801;