rs270723

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF220	NM_018150.4	c.626-93442C>A		intron_variant		ENST00000361799.7	NP_060620.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF220	ENST00000361799.7	c.626-93442C>A		intron_variant		1	NM_018150.4	ENSP00000354872	P1
RNF220	ENST00000355387.6	c.626-93442C>A		intron_variant		1		ENSP00000347548	P1

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

Gnomad4 AFR AF: 0.890

Gnomad4 AMR AF: 0.989

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.979

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.33
DANN	Benign	0.38

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: rs270723; hg19: chr1-44986395;