rs6851075

Positions:

• chr4-39366034-T-C
• chr4-39366034-T-G

Variant summary

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

The NM_002913.5(RFC1):​c.3+205A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 150,178 control chromosomes in the GnomAD database, including 7,694 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 0.32 (7694 hom., cov: 32)
• Consequence: RFC1 NM_002913.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RFC1	NM_002913.5	c.3+205A>G		intron_variant		ENST00000349703.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFC1	ENST00000349703.7	c.3+205A>G		intron_variant		1	NM_002913.5	P4

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48158 AN: 150066 Hom.: 7689 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.321 AC: 48164 AN: 150178 Hom.: 7694 Cov.: 32 AF XY: 0.317 AC XY: 23243 AN XY: 73298

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.315

Alfa AF: 0.327 Hom.: 10980

Bravo AF: 0.313

Asia WGS AF: 0.226 AC: 786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.42
DANN	Benign	0.66

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: rs6851075; hg19: chr4-39367654;