rs308901

Positions:

• chr2-86619366-T-C

Variant summary

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

The NM_005667.4(RNF103):​c.366+964A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 152,072 control chromosomes in the GnomAD database, including 43,099 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 0.75 (43099 hom., cov: 31)
• Consequence: RNF103 NM_005667.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.832

Genes affected

RNF103 (HGNC:12859): (ring finger protein 103) The protein encoded by this gene contains a RING-H2 finger, a motif known to be involved in protein-protein and protein-DNA interactions. This gene is highly expressed in normal cerebellum, but not in the cerebral cortex. The expression of the rat counterpart in the frontal cortex and hippocampus was shown to be induced by elctroconvulsive treatment (ECT) as well as chronic antidepressant treatment, suggesting that this gene may be a molecular target for ECT and antidepressants. The protein is a ubiquitin ligase that functions in the endoplasmic reticulum-associated degradation pathway. Alternative splicing of this gene results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream CHMP3 (charged multivesicular body protein 3) gene. [provided by RefSeq, Oct 2011]

RNF103-CHMP3 (HGNC:38847): (RNF103-CHMP3 readthrough) This locus represents naturally occurring read-through transcription between the neighboring RNF103 (ring finger protein 103) and CHMP3 (charged multivesicular body protein 3) genes. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Oct 2011]

RNF103 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF103	NM_005667.4	c.366+964A>G		intron_variant		ENST00000237455.5	NP_005658.1
RNF103	NM_001198951.1	c.354+964A>G		intron_variant			NP_001185880.1
RNF103-CHMP3	NM_001198954.1	c.132+964A>G		intron_variant			NP_001185883.1
RNF103	NM_001198952.2	c.366+964A>G		intron_variant			NP_001185881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF103	ENST00000237455.5	c.366+964A>G		intron_variant		1	NM_005667.4	ENSP00000237455.4
RNF103-CHMP3	ENST00000604011.5	c.132+964A>G		intron_variant		2		ENSP00000474823.1

Frequencies

GnomAD3 genomes AF: 0.750 AC: 113953 AN: 151954 Hom.: 43053 Cov.: 31

Gnomad AFR AF: 0.810

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.760

Gnomad EAS AF: 0.926

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.714

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

GnomAD4 genome AF: 0.750 AC: 114058 AN: 152072 Hom.: 43099 Cov.: 31 AF XY: 0.745 AC XY: 55415 AN XY: 74354

Gnomad4 AFR AF: 0.811

Gnomad4 AMR AF: 0.704

Gnomad4 ASJ AF: 0.760

Gnomad4 EAS AF: 0.925

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.732

Gnomad4 NFE AF: 0.725

Gnomad4 OTH AF: 0.716

Alfa AF: 0.727 Hom.: 50681

Bravo AF: 0.758

Asia WGS AF: 0.754 AC: 2617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.6
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: rs308901; hg19: chr2-86846489;