NM_018150.4:c.758+2371G>T

Variant names:

• chr1-44616668-G-T
• rs11585508
• NM_018150.4:c.758+2371G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018150.4(RNF220):​c.758+2371G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
• Consequence: RNF220 NM_018150.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.678
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

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.758+2371G>T		intron	N/A	NP_060620.2
	RNF220	NM_001376486.1		c.758+2371G>T		intron	N/A	NP_001363415.1
	RNF220	NM_001376487.1		c.758+2371G>T		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.758+2371G>T		intron	N/A	ENSP00000354872.2
	RNF220	ENST00000355387.6	TSL:1	c.758+2371G>T		intron	N/A	ENSP00000347548.2
	RNF220	ENST00000496262.1	TSL:2	n.33+2371G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 27426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.7
DANN	Benign	0.63
PhyloP100		0.68

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: rs11585508; hg19: chr1-45082340;