rs17288757

chr4-39292459-G-A

Variant summary

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

The NM_002913.5(RFC1):c.2955-607C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0396 in 152,122 control chromosomes in the GnomAD database, including 173 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 0.040 (173 hom., cov: 32)
• Consequence: RFC1 NM_002913.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RFC1	NM_002913.5	c.2955-607C>T		intron_variant		ENST00000349703.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFC1	ENST00000349703.7	c.2955-607C>T		intron_variant		1	NM_002913.5	P4
RFC1	ENST00000381897.5	c.2958-607C>T		intron_variant		1		A2
RFC1	ENST00000510783.5	n.170-607C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0397 AC: 6028 AN: 152004 Hom.: 173 Cov.: 32

Gnomad AFR AF: 0.0101

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.0382

Gnomad ASJ AF: 0.0666

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0222

Gnomad FIN AF: 0.0552

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0563

Gnomad OTH AF: 0.0406

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

GnomAD4 genome AF: 0.0396 AC: 6025 AN: 152122 Hom.: 173 Cov.: 32 AF XY: 0.0385 AC XY: 2860 AN XY: 74360

Gnomad4 AFR AF: 0.0100

Gnomad4 AMR AF: 0.0382

Gnomad4 ASJ AF: 0.0666

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0224

Gnomad4 FIN AF: 0.0552

Gnomad4 NFE AF: 0.0562

Gnomad4 OTH AF: 0.0402

Alfa AF: 0.0504 Hom.: 34

Bravo AF: 0.0381

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.0
Dann	Benign	0.76

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: rs17288757; hg19: chr4-39294079;