rs270765

Variant names:

• chr1-44557743-T-C
• rs270765
• NM_018150.4:c.626-56422T>C

Variant summary

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

The NM_018150.4(RNF220):​c.626-56422T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0891 in 152,264 control chromosomes in the GnomAD database, including 824 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 0.089 (824 hom., cov: 32)
• Consequence: RNF220 NM_018150.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.138
• Publications: 5 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018150.4. 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
	RNF220	NM_018150.4	MANE Select	c.626-56422T>C		intron	N/A	NP_060620.2
	RNF220	NM_001376486.1		c.626-56422T>C		intron	N/A	NP_001363415.1
	RNF220	NM_001376487.1		c.626-56422T>C		intron	N/A	NP_001363416.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF220	ENST00000361799.7	TSL:1 MANE Select	c.626-56422T>C		intron	N/A	ENSP00000354872.2
	RNF220	ENST00000355387.6	TSL:1	c.626-56422T>C		intron	N/A	ENSP00000347548.2

Frequencies

GnomAD3 genomes AF: 0.0891 AC: 13562 AN: 152146 Hom.: 826 Cov.: 32

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0962

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0994

Gnomad OTH AF: 0.0994

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

GnomAD4 genome AF: 0.0891 AC: 13563 AN: 152264 Hom.: 824 Cov.: 32 AF XY: 0.0927 AC XY: 6901 AN XY: 74454

African (AFR) AF: 0.0276 AC: 1148 AN: 41566

American (AMR) AF: 0.0960 AC: 1468 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 483 AN: 3472

East Asian (EAS) AF: 0.258 AC: 1336 AN: 5184

South Asian (SAS) AF: 0.155 AC: 747 AN: 4824

European-Finnish (FIN) AF: 0.122 AC: 1297 AN: 10602

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.0994 AC: 6757 AN: 67998

Other (OTH) AF: 0.0998 AC: 211 AN: 2114

Alfa AF: 0.100 Hom.: 1576

Bravo AF: 0.0843

Asia WGS AF: 0.167 AC: 579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.2
DANN	Benign	0.66
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: rs270765; hg19: chr1-45023415; COSMIC: COSV62405583;