NM_002913.5:c.3+1269A>G

Variant names:

• chr4-39364970-T-C
• rs6844176
• NM_002913.5:c.3+1269A>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+1269A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,796 control chromosomes in the GnomAD database, including 12,980 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 0.38 (12980 hom., cov: 29)
• Consequence: RFC1 NM_002913.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFC1	NM_002913.5	c.3+1269A>G		intron_variant	Intron 1 of 24	ENST00000349703.7	NP_002904.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RFC1	ENST00000349703.7	c.3+1269A>G		intron_variant	Intron 1 of 24	1	NM_002913.5	ENSP00000261424.4

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57361 AN: 151678 Hom.: 12977 Cov.: 29

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.378 AC: 57365 AN: 151796 Hom.: 12980 Cov.: 29 AF XY: 0.383 AC XY: 28413 AN XY: 74156

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.547

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.586

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.422

Alfa AF: 0.459 Hom.: 26918

Bravo AF: 0.379

Asia WGS AF: 0.509 AC: 1772 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs6844176; hg19: chr4-39366590;