rs270723

Variant names:

• chr1-44520723-C-A
• rs270723
• NM_018150.4:c.626-93442C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-44520723-C-A
• chr1-44520723-C-G
• chr1-44520723-C-T

Variant summary

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

The NM_018150.4(RNF220):​c.626-93442C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.968 in 152,286 control chromosomes in the GnomAD database, including 71,564 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 0.97 (71564 hom., cov: 31)
• Consequence: RNF220 NM_018150.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.579
• Publications: 1 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF220	NM_018150.4	MANE Select	c.626-93442C>A		intron	N/A	NP_060620.2
	RNF220	NM_001376486.1		c.626-93442C>A		intron	N/A	NP_001363415.1
	RNF220	NM_001376487.1		c.626-93442C>A		intron	N/A	NP_001363416.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF220	ENST00000361799.7	TSL:1 MANE Select	c.626-93442C>A		intron	N/A	ENSP00000354872.2
	RNF220	ENST00000355387.6	TSL:1	c.626-93442C>A		intron	N/A	ENSP00000347548.2
	RNF220	ENST00000925767.1		c.626-93442C>A		intron	N/A	ENSP00000595826.1

Frequencies

GnomAD3 genomes AF: 0.968 AC: 147349 AN: 152168 Hom.: 71513 Cov.: 31

Gnomad AFR AF: 0.890

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.989

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.979

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

GnomAD4 genome AF: 0.968 AC: 147458 AN: 152286 Hom.: 71564 Cov.: 31 AF XY: 0.969 AC XY: 72185 AN XY: 74464

African (AFR) AF: 0.890 AC: 36931 AN: 41516

American (AMR) AF: 0.989 AC: 15137 AN: 15302

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5190 AN: 5190

South Asian (SAS) AF: 0.999 AC: 4821 AN: 4824

European-Finnish (FIN) AF: 1.00 AC: 10622 AN: 10622

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68008 AN: 68038

Other (OTH) AF: 0.979 AC: 2072 AN: 2116

Alfa AF: 0.984 Hom.: 8587

Bravo AF: 0.964

Asia WGS AF: 0.994 AC: 3456 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.33
DANN	Benign	0.38
PhyloP100		-0.58
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: rs270723; hg19: chr1-44986395;