rs11585508

Positions:

• chr1-44616668-G-A
• chr1-44616668-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018150.4(RNF220):​c.758+2371G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 151,680 control chromosomes in the GnomAD database, including 17,877 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 0.47 (17877 hom., cov: 30)
• Consequence: RNF220 NM_018150.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.678

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF220	NM_018150.4	c.758+2371G>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.758+2371G>A		intron_variant		1	NM_018150.4	ENSP00000354872	P1
RNF220	ENST00000355387.6	c.758+2371G>A		intron_variant		1		ENSP00000347548	P1
RNF220	ENST00000496262.1	n.33+2371G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71895 AN: 151562 Hom.: 17875 Cov.: 30

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.474 AC: 71920 AN: 151680 Hom.: 17877 Cov.: 30 AF XY: 0.468 AC XY: 34691 AN XY: 74112

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.562

Gnomad4 NFE AF: 0.567

Gnomad4 OTH AF: 0.478

Alfa AF: 0.537 Hom.: 21517

Bravo AF: 0.454

Asia WGS AF: 0.301 AC: 1050 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.2
DANN	Benign	0.55

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: rs11585508; hg19: chr1-45082340; COSMIC: COSV62410132;