rs16851720

Positions:

• chr3-141744456-A-C

Variant summary

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

The NM_014245.5(RNF7):​c.224-703A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 151,920 control chromosomes in the GnomAD database, including 3,571 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 0.21 (3571 hom., cov: 32)
• Consequence: RNF7 NM_014245.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.676

Genes affected

RNF7 (HGNC:10070): (ring finger protein 7) The protein encoded by this gene is a highly conserved ring finger protein. It is an essential subunit of SKP1-cullin/CDC53-F box protein ubiquitin ligases, which are a part of the protein degradation machinery important for cell cycle progression and signal transduction. This protein interacts with, and is a substrate of, casein kinase II (CSNK2A1/CKII). The phosphorylation of this protein by CSNK2A1 has been shown to promote the degradation of IkappaBalpha (CHUK/IKK-alpha/IKBKA) and p27Kip1(CDKN1B). Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF7	NM_014245.5	c.224-703A>C		intron_variant		ENST00000273480.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF7	ENST00000273480.4	c.224-703A>C		intron_variant		1	NM_014245.5	P1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31854 AN: 151802 Hom.: 3562 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.0692

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.210 AC: 31890 AN: 151920 Hom.: 3571 Cov.: 32 AF XY: 0.204 AC XY: 15178 AN XY: 74260

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.0689

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.206

Alfa AF: 0.199 Hom.: 2979

Bravo AF: 0.212

Asia WGS AF: 0.114 AC: 399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.4
DANN	Benign	0.73

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: rs16851720; hg19: chr3-141463298;