ENST00000910311.1:c.-48G>A

Variant names:

• chr1-185044870-G-A
• rs3753573
• ENST00000910311.1:c.-48G>A

Variant summary

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

The ENST00000910311.1(RNF2):​c.-48G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00691 in 152,240 control chromosomes in the GnomAD database, including 32 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 0.0069 (32 hom., cov: 32)
• Consequence: RNF2 ENST00000910311.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 5 publications found

Genes affected

RNF2 (HGNC:10061): (ring finger protein 2) Polycomb group (PcG) of proteins form the multiprotein complexes that are important for the transcription repression of various genes involved in development and cell proliferation. The protein encoded by this gene is one of the PcG proteins. It has been shown to interact with, and suppress the activity of, transcription factor CP2 (TFCP2/CP2). Studies of the mouse counterpart suggested the involvement of this gene in the specification of anterior-posterior axis, as well as in cell proliferation in early development. This protein was also found to interact with huntingtin interacting protein 2 (HIP2), an ubiquitin-conjugating enzyme, and possess ubiquitin ligase activity. [provided by RefSeq, Jul 2008]

RNF2 Gene-Disease associations (from GenCC):

• Luo-Schoch-Yamamoto syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0812 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000910311.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF2	ENST00000910311.1		c.-48G>A		5_prime_UTR	Exon 1 of 7	ENSP00000580370.1

Frequencies

GnomAD3 genomes AF: 0.00691 AC: 1051 AN: 152122 Hom.: 32 Cov.: 32

Gnomad AFR AF: 0.00560

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00380

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.0881

Gnomad SAS AF: 0.0352

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00169

Gnomad OTH AF: 0.00478

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

GnomAD4 genome AF: 0.00691 AC: 1052 AN: 152240 Hom.: 32 Cov.: 32 AF XY: 0.00762 AC XY: 567 AN XY: 74434

African (AFR) AF: 0.00564 AC: 234 AN: 41522

American (AMR) AF: 0.00373 AC: 57 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.0879 AC: 455 AN: 5178

South Asian (SAS) AF: 0.0354 AC: 171 AN: 4826

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10612

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00171 AC: 116 AN: 68014

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00464 Hom.: 26

Bravo AF: 0.00640

Asia WGS AF: 0.0470 AC: 163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.093
DANN	Benign	0.45
PhyloP100		-1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3753573; hg19: chr1-185014002;