rs2306597

Positions:

• chr4-39295580-G-A

Variant summary

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

The ENST00000349703.7(RFC1):​c.2954+34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,542,264 control chromosomes in the GnomAD database, including 30,292 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 0.17 (2461 hom., cov: 32)
  • Exomes 𝑓: 0.20 (27831 hom.)
• Consequence: RFC1 ENST00000349703.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.383

Genes affected

RFC1 (HGNC:9969): (replication factor C subunit 1) This gene encodes the large subunit of replication factor C, a five subunit DNA polymerase accessory protein, which is a DNA-dependent ATPase required for eukaryotic DNA replication and repair. The large subunit acts as an activator of DNA polymerases, binds to the 3' end of primers, and promotes coordinated synthesis of both strands. It may also have a role in telomere stability. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Mar 2011]

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 = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RFC1	NM_002913.5	c.2954+34C>T		intron_variant		ENST00000349703.7	NP_002904.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFC1	ENST00000349703.7	c.2954+34C>T		intron_variant		1	NM_002913.5	ENSP00000261424	P4
RFC1	ENST00000381897.5	c.2957+34C>T		intron_variant		1		ENSP00000371321	A2
RFC1	ENST00000510783.5	n.169+34C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26331 AN: 151750 Hom.: 2460 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.0664

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.167

GnomAD3 exomes AF: 0.183 AC: 40399 AN: 220356 Hom.: 4100 AF XY: 0.189 AC XY: 22471 AN XY: 119190

Gnomad AFR exome AF: 0.115

Gnomad AMR exome AF: 0.130

Gnomad ASJ exome AF: 0.180

Gnomad EAS exome AF: 0.0610

Gnomad SAS exome AF: 0.221

Gnomad FIN exome AF: 0.242

Gnomad NFE exome AF: 0.206

Gnomad OTH exome AF: 0.176

GnomAD4 exome AF: 0.196 AC: 272166 AN: 1390396 Hom.: 27831 Cov.: 26 AF XY: 0.197 AC XY: 135438 AN XY: 687164

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.130

Gnomad4 ASJ exome AF: 0.177

Gnomad4 EAS exome AF: 0.0665

Gnomad4 SAS exome AF: 0.219

Gnomad4 FIN exome AF: 0.235

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.190

GnomAD4 genome AF: 0.173 AC: 26331 AN: 151868 Hom.: 2461 Cov.: 32 AF XY: 0.175 AC XY: 12954 AN XY: 74190

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.0664

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.165

Alfa AF: 0.195 Hom.: 4334

Bravo AF: 0.162

Asia WGS AF: 0.135 AC: 470 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	0.066
DANN	Benign	0.79

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: rs2306597; hg19: chr4-39297200; COSMIC: COSV62899362; COSMIC: COSV62899362;