rs4388643

Positions:

• chr1-145808023-G-C
• chr1-145808023-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF115	NM_014455.4	c.102+15749C>G		intron_variant		ENST00000582693.5
RNF115	XM_047418027.1	c.-83+15749C>G		intron_variant
RNF115	XM_047418028.1	c.102+15749C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF115	ENST00000582693.5	c.102+15749C>G		intron_variant		1	NM_014455.4	P1

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

Gnomad4 AFR AF: 0.895

Gnomad4 AMR AF: 0.866

Gnomad4 ASJ AF: 0.872

Gnomad4 EAS AF: 0.855

Gnomad4 SAS AF: 0.823

Gnomad4 FIN AF: 0.839

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.853

Alfa AF: 0.767 Hom.: 2616

Bravo AF: 0.842

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	0.80

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: rs4388643; hg19: -;