rs10491117

chr17-35065066-T-C

Variant summary

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

The NR_037714.1(RAD51L3-RFFL):n.655+36135A>G variant causes a intron, non coding transcript 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: RAD51L3-RFFL NR_037714.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

Genes affected

RAD51L3-RFFL (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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD51L3-RFFL	NR_037714.1	n.655+36135A>G		intron_variant, non_coding_transcript_variant
RFFL	NR_037713.2	n.122+24039A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFFL	ENST00000315249.11	c.-9+24039A>G		intron_variant		2		P4
RFFL	ENST00000414419.6	c.-9+23675A>G		intron_variant		4
RFFL	ENST00000447669.6	c.-9+4228A>G		intron_variant		5		P4

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

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.0334

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.0420

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00259

Gnomad4 OTH AF: 0.0682

Alfa AF: 0.0929 Hom.: 286

Bravo AF: 0.104

Asia WGS AF: 0.105 AC: 363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	4.7
Dann	Benign	0.62

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: rs10491117; hg19: chr17-33392085;