rs10491117

Variant names:

• chr17-35065066-T-C
• rs10491117
• ENST00000593039.5:c.426+36135A>G

Variant summary

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

The ENST00000593039.5(ENSG00000267618):​c.426+36135A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0919 in 152,192 control chromosomes in the GnomAD database, including 1,961 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 0.092 (1961 hom., cov: 31)
• Consequence: ENSG00000267618 ENST00000593039.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 0 publications found

Genes affected

ENSG00000267618 (HGNC:):

RFFL (HGNC:24821): (ring finger and FYVE like domain containing E3 ubiquitin protein ligase) Enables enzyme binding activity; p53 binding activity; and ubiquitin protein ligase activity. Involved in cellular protein metabolic process; negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis; and negative regulation of signal transduction. Located in endosome membrane and plasma membrane. [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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000593039.5. 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
	RFFL	NR_037713.2		n.122+24039A>G		intron	N/A
	RAD51L3-RFFL	NR_037714.1		n.655+36135A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000267618	ENST00000593039.5	TSL:2	c.426+36135A>G		intron	N/A	ENSP00000466834.1	K7EN88
	RFFL	ENST00000948502.1		c.-9+24039A>G		intron	N/A	ENSP00000618561.1
	RFFL	ENST00000910974.1		c.-9+24039A>G		intron	N/A	ENSP00000581033.1

Frequencies

GnomAD3 genomes AF: 0.0917 AC: 13950 AN: 152074 Hom.: 1951 Cov.: 31

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0336

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.0426

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.00259

Gnomad OTH AF: 0.0636

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

GnomAD4 genome AF: 0.0919 AC: 13986 AN: 152192 Hom.: 1961 Cov.: 31 AF XY: 0.0902 AC XY: 6710 AN XY: 74394

African (AFR) AF: 0.299 AC: 12375 AN: 41456

American (AMR) AF: 0.0334 AC: 511 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.108 AC: 561 AN: 5182

South Asian (SAS) AF: 0.0420 AC: 203 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.00259 AC: 176 AN: 68030

Other (OTH) AF: 0.0682 AC: 144 AN: 2112

Alfa AF: 0.100 Hom.: 320

Bravo AF: 0.104

Asia WGS AF: 0.105 AC: 363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.7
DANN	Benign	0.62
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10491117;

hg19: chr17-33392085;