rs3866642

Variant names:

• chr1-44420250-T-C
• rs3866642
• NM_018150.4:c.625+7528T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-44420250-T-C
• chr1-44420250-T-G

Variant summary

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

The NM_018150.4(RNF220):​c.625+7528T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 152,050 control chromosomes in the GnomAD database, including 23,548 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 0.55 (23548 hom., cov: 33)
• Consequence: RNF220 NM_018150.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950
• Publications: 3 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 (SAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF220	NM_018150.4	c.625+7528T>C		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.625+7528T>C		intron_variant	Intron 2 of 14	1	NM_018150.4	ENSP00000354872.2
RNF220	ENST00000355387.6	c.625+7528T>C		intron_variant	Intron 2 of 14	1		ENSP00000347548.2

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83565 AN: 151930 Hom.: 23540 Cov.: 33

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.550 AC: 83594 AN: 152050 Hom.: 23548 Cov.: 33 AF XY: 0.552 AC XY: 40999 AN XY: 74324

African (AFR) AF: 0.431 AC: 17878 AN: 41440

American (AMR) AF: 0.578 AC: 8829 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2337 AN: 3472

East Asian (EAS) AF: 0.456 AC: 2362 AN: 5176

South Asian (SAS) AF: 0.613 AC: 2957 AN: 4822

European-Finnish (FIN) AF: 0.595 AC: 6284 AN: 10554

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41109 AN: 67982

Other (OTH) AF: 0.563 AC: 1188 AN: 2112

Alfa AF: 0.583 Hom.: 14150

Bravo AF: 0.539

Asia WGS AF: 0.550 AC: 1917 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	13
DANN	Benign	0.53
PhyloP100		0.095
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3866642; hg19: chr1-44885922;