rs3135677

Positions:

• chr7-74240801-T-C

Variant summary

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

The NM_181471.3(RFC2):​c.536-706A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 151,814 control chromosomes in the GnomAD database, including 6,607 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 0.29 (6607 hom., cov: 32)
• Consequence: RFC2 NM_181471.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

Genes affected

RFC2 (HGNC:9970): (replication factor C subunit 2) This gene encodes a member of the activator 1 small subunits family. The elongation of primed DNA templates by DNA polymerase delta and epsilon requires the action of the accessory proteins, proliferating cell nuclear antigen (PCNA) and replication factor C (RFC). Replication factor C, also called activator 1, is a protein complex consisting of five distinct subunits. This gene encodes the 40 kD subunit, which has been shown to be responsible for binding ATP and may help promote cell survival. Disruption of this gene is associated with Williams syndrome. Alternatively spliced transcript variants encoding distinct isoforms have been described. A pseudogene of this gene has been defined on chromosome 2. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RFC2	NM_181471.3	c.536-706A>G		intron_variant		ENST00000055077.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFC2	ENST00000055077.8	c.536-706A>G		intron_variant		1	NM_181471.3	P1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44328 AN: 151696 Hom.: 6606 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.292 AC: 44328 AN: 151814 Hom.: 6607 Cov.: 32 AF XY: 0.288 AC XY: 21395 AN XY: 74186

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.288

Alfa AF: 0.306 Hom.: 1453

Bravo AF: 0.296

Asia WGS AF: 0.224 AC: 780 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.57
DANN	Benign	0.35

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: rs3135677; hg19: chr7-73655131;