11-117252457-T-C

Variant names:

• chr11-117252457-T-C
• rs528508
• NM_207343.4:c.959+5509T>C

Variant summary

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

The NM_207343.4(RNF214):​c.959+5509T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 152,066 control chromosomes in the GnomAD database, including 14,096 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 0.42 (14096 hom., cov: 32)
• Consequence: RNF214 NM_207343.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 2 publications found

Genes affected

RNF214 (HGNC:25335): (ring finger protein 214) Predicted to enable ubiquitin-protein transferase activity. Predicted to be involved in protein ubiquitination. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207343.4. 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
	RNF214	NM_207343.4	MANE Select	c.959+5509T>C		intron	N/A	NP_997226.2
	RNF214	NM_001077239.2		c.959+5509T>C		intron	N/A	NP_001070707.1
	RNF214	NM_001278249.2		c.494+5509T>C		intron	N/A	NP_001265178.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF214	ENST00000300650.9	TSL:1 MANE Select	c.959+5509T>C		intron	N/A	ENSP00000300650.4
	RNF214	ENST00000531452.5	TSL:1	c.959+5509T>C		intron	N/A	ENSP00000431643.1
	RNF214	ENST00000852075.1		c.959+5509T>C		intron	N/A	ENSP00000522134.1

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64205 AN: 151948 Hom.: 14085 Cov.: 32

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.445

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

GnomAD4 genome AF: 0.422 AC: 64244 AN: 152066 Hom.: 14096 Cov.: 32 AF XY: 0.432 AC XY: 32140 AN XY: 74332

African (AFR) AF: 0.410 AC: 17007 AN: 41474

American (AMR) AF: 0.540 AC: 8245 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1532 AN: 3472

East Asian (EAS) AF: 0.648 AC: 3354 AN: 5172

South Asian (SAS) AF: 0.612 AC: 2954 AN: 4828

European-Finnish (FIN) AF: 0.427 AC: 4508 AN: 10566

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.371 AC: 25230 AN: 67984

Other (OTH) AF: 0.448 AC: 946 AN: 2110

Alfa AF: 0.406 Hom.: 2774

Bravo AF: 0.429

Asia WGS AF: 0.633 AC: 2202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.068
DANN	Benign	0.37
PhyloP100		-1.2
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: rs528508; hg19: chr11-117123173;