1-145808023-G-C

Variant names:

• chr1-145808023-G-C
• rs4388643
• NM_014455.4:c.102+15749C>G

Variant summary

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

The NM_014455.4(RNF115):​c.102+15749C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 152,148 control chromosomes in the GnomAD database, including 53,201 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 0.83 (53201 hom., cov: 31)
• Consequence: RNF115 NM_014455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.537
• Publications: 5 publications found

Genes affected

RNF115 (HGNC:18154): (ring finger protein 115) Enables ubiquitin-protein transferase activity. Involved in negative regulation of epidermal growth factor receptor signaling pathway; protein autoubiquitination; and ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (Cadd=0.795).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014455.4. 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
	RNF115	NM_014455.4	MANE Select	c.102+15749C>G		intron	N/A	NP_055270.1	Q9Y4L5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF115	ENST00000582693.5	TSL:1 MANE Select	c.102+15749C>G		intron	N/A	ENSP00000463650.1	Q9Y4L5
	RNF115	ENST00000891105.1		c.102+15749C>G		intron	N/A	ENSP00000561164.1
	RNF115	ENST00000891106.1		c.102+15749C>G		intron	N/A	ENSP00000561165.1

Frequencies

GnomAD3 genomes AF: 0.834 AC: 126866 AN: 152030 Hom.: 53164 Cov.: 31

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.899

Gnomad AMR AF: 0.866

Gnomad ASJ AF: 0.872

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.839

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.851

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

GnomAD4 genome AF: 0.834 AC: 126953 AN: 152148 Hom.: 53201 Cov.: 31 AF XY: 0.838 AC XY: 62289 AN XY: 74370

African (AFR) AF: 0.895 AC: 37152 AN: 41528

American (AMR) AF: 0.866 AC: 13241 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.872 AC: 3025 AN: 3470

East Asian (EAS) AF: 0.855 AC: 4425 AN: 5176

South Asian (SAS) AF: 0.823 AC: 3963 AN: 4814

European-Finnish (FIN) AF: 0.839 AC: 8888 AN: 10592

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.785 AC: 53385 AN: 67970

Other (OTH) AF: 0.853 AC: 1804 AN: 2114

Alfa AF: 0.767 Hom.: 2616

Bravo AF: 0.842

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
CADD	Benign	0.80
PhyloP100		-0.54

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: rs4388643;