rs17288033

chr4-39335651-G-C

Variant summary

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

The NM_002913.5(RFC1):c.331+6694C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0753 in 152,128 control chromosomes in the GnomAD database, including 569 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 0.075 (569 hom., cov: 32)
• Consequence: RFC1 NM_002913.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630

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 = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RFC1	NM_002913.5	c.331+6694C>G		intron_variant		ENST00000349703.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFC1	ENST00000349703.7	c.331+6694C>G		intron_variant		1	NM_002913.5	P4

Frequencies

GnomAD3 genomes AF: 0.0754 AC: 11460 AN: 152008 Hom.: 570 Cov.: 32

Gnomad AFR AF: 0.0198

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0761

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0195

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0945

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

GnomAD4 genome AF: 0.0753 AC: 11450 AN: 152128 Hom.: 569 Cov.: 32 AF XY: 0.0760 AC XY: 5652 AN XY: 74352

Gnomad4 AFR AF: 0.0197

Gnomad4 AMR AF: 0.0760

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0191

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.0935

Alfa AF: 0.0891 Hom.: 92

Bravo AF: 0.0697

Asia WGS AF: 0.0110 AC: 39 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	1.2
Dann	Benign	0.40

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: rs17288033; hg19: chr4-39337271;