rs270724

Variant names:

• chr1-44525606-G-A
• rs270724
• NM_018150.4:c.626-88559G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018150.4(RNF220):​c.626-88559G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,082 control chromosomes in the GnomAD database, including 2,176 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 0.15 (2176 hom., cov: 32)
• Consequence: RNF220 NM_018150.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145
• Publications: 2 publications found

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]

RNF220 Gene-Disease associations (from GenCC):

• leukodystrophy, hypomyelinating, 23, with ataxia, deafness, liver dysfunction, and dilated cardiomyopathy

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF220	NM_018150.4	c.626-88559G>A		intron_variant	Intron 2 of 14	ENST00000361799.7	NP_060620.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF220	ENST00000361799.7	c.626-88559G>A		intron_variant	Intron 2 of 14	1	NM_018150.4	ENSP00000354872.2
RNF220	ENST00000355387.6	c.626-88559G>A		intron_variant	Intron 2 of 14	1		ENSP00000347548.2

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22985 AN: 151962 Hom.: 2169 Cov.: 32

Gnomad AFR AF: 0.0456

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.0674

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.151 AC: 23009 AN: 152082 Hom.: 2176 Cov.: 32 AF XY: 0.151 AC XY: 11201 AN XY: 74342

African (AFR) AF: 0.0458 AC: 1900 AN: 41480

American (AMR) AF: 0.216 AC: 3294 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 633 AN: 3464

East Asian (EAS) AF: 0.0676 AC: 350 AN: 5178

South Asian (SAS) AF: 0.147 AC: 711 AN: 4822

European-Finnish (FIN) AF: 0.165 AC: 1743 AN: 10576

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13776 AN: 67984

Other (OTH) AF: 0.171 AC: 362 AN: 2112

Alfa AF: 0.189 Hom.: 9421

Bravo AF: 0.154

Asia WGS AF: 0.104 AC: 361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.5
DANN	Benign	0.60
PhyloP100		0.14
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: rs270724; hg19: chr1-44991278; COSMIC: COSV62405545;