rs3744358

chr17-35009895-T-G

Variant summary

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

The NM_001017368.2(RFFL):c.*2073A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,578 control chromosomes in the GnomAD database, including 5,779 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 0.26 (5766 hom., cov: 32)
  • Exomes 𝑓: 0.27 (13 hom.)
• Consequence: RFFL NM_001017368.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.119

Genes affected

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]

RAD51L3-RFFL (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RFFL	NM_001017368.2	c.*2073A>C		3_prime_UTR_variant	7/7	ENST00000394597.7
RAD51L3-RFFL	NR_037714.1	n.3121A>C		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFFL	ENST00000394597.7	c.*2073A>C		3_prime_UTR_variant	7/7	1	NM_001017368.2	P4
RFFL	ENST00000315249.11	c.*2073A>C		3_prime_UTR_variant	7/7	2		P4
RFFL	ENST00000584655.5	c.*2073A>C		3_prime_UTR_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40218 AN: 152026 Hom.: 5766 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.0961

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.293

GnomAD4 exome AF: 0.267 AC: 116 AN: 434 Hom.: 13 Cov.: 0 AF XY: 0.267 AC XY: 70 AN XY: 262

Gnomad4 FIN exome AF: 0.268

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.264 AC: 40228 AN: 152144 Hom.: 5766 Cov.: 32 AF XY: 0.263 AC XY: 19572 AN XY: 74360

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.0957

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.291

Alfa AF: 0.299 Hom.: 9235

Bravo AF: 0.272

Asia WGS AF: 0.166 AC: 577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	5.4
Dann	Benign	0.82

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: rs3744358; hg19: chr17-33336914;