3-141744456-A-C

Variant names:

• chr3-141744456-A-C
• rs16851720
• NM_014245.5:c.224-703A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 25 publications found

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]

ENSG00000285558 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014245.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF7	NM_014245.5	MANE Select	c.224-703A>C		intron	N/A	NP_055060.1
	RNF7	NM_001201370.2		c.176-703A>C		intron	N/A	NP_001188299.1
	RNF7	NM_183237.3		c.217-703A>C		intron	N/A	NP_899060.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF7	ENST00000273480.4	TSL:1 MANE Select	c.224-703A>C		intron	N/A	ENSP00000273480.3
	RNF7	ENST00000477012.5	TSL:1	n.*161-703A>C		intron	N/A	ENSP00000419339.1
	ENSG00000285558	ENST00000648835.1		n.43+5940A>C		intron	N/A	ENSP00000498049.1

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

African (AFR) AF: 0.274 AC: 11357 AN: 41382

American (AMR) AF: 0.171 AC: 2610 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 854 AN: 3470

East Asian (EAS) AF: 0.0689 AC: 357 AN: 5178

South Asian (SAS) AF: 0.166 AC: 802 AN: 4818

European-Finnish (FIN) AF: 0.146 AC: 1538 AN: 10538

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13619 AN: 67972

Other (OTH) AF: 0.206 AC: 433 AN: 2102

Alfa AF: 0.203 Hom.: 8911

Bravo AF: 0.212

Asia WGS AF: 0.114 AC: 399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.4
DANN	Benign	0.73
PhyloP100		0.68
Mutation Taster		=100/0	polymorphism (auto)

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: rs16851720; hg19: chr3-141463298;