4-39299985-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002913.5(RFC1):c.2808+36C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 1,211,812 control chromosomes in the GnomAD database, including 125,436 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.51 (21680 hom., cov: 33)
  • Exomes 𝑓: 0.44 (103756 hom.)
• Consequence: RFC1 NM_002913.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.21

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 4-39299985-G-C is Benign according to our data. Variant chr4-39299985-G-C is described in ClinVar as [Benign]. Clinvar id is 1327948.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RFC1	NM_002913.5	c.2808+36C>G		intron_variant		ENST00000349703.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFC1	ENST00000349703.7	c.2808+36C>G		intron_variant		1	NM_002913.5	P4
RFC1	ENST00000381897.5	c.2811+36C>G		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77788 AN: 152034 Hom.: 21640 Cov.: 33

Gnomad AFR AF: 0.742

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.485

GnomAD3 exomes AF: 0.433 AC: 106256 AN: 245524 Hom.: 24106 AF XY: 0.429 AC XY: 56897 AN XY: 132758

Gnomad AFR exome AF: 0.746

Gnomad AMR exome AF: 0.333

Gnomad ASJ exome AF: 0.471

Gnomad EAS exome AF: 0.357

Gnomad SAS exome AF: 0.404

Gnomad FIN exome AF: 0.451

Gnomad NFE exome AF: 0.431

Gnomad OTH exome AF: 0.430

GnomAD4 exome AF: 0.438 AC: 463743 AN: 1059660 Hom.: 103756 Cov.: 14 AF XY: 0.435 AC XY: 237170 AN XY: 545288

Gnomad4 AFR exome AF: 0.745

Gnomad4 AMR exome AF: 0.346

Gnomad4 ASJ exome AF: 0.464

Gnomad4 EAS exome AF: 0.365

Gnomad4 SAS exome AF: 0.409

Gnomad4 FIN exome AF: 0.446

Gnomad4 NFE exome AF: 0.436

Gnomad4 OTH exome AF: 0.453

GnomAD4 genome AF: 0.512 AC: 77882 AN: 152152 Hom.: 21680 Cov.: 33 AF XY: 0.507 AC XY: 37686 AN XY: 74352

Gnomad4 AFR AF: 0.742

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.472

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.429

Gnomad4 OTH AF: 0.486

Alfa AF: 0.366 Hom.: 1575

Bravo AF: 0.517

Asia WGS AF: 0.413 AC: 1436 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	14
Dann	Benign	0.54

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: rs2066788; hg19: chr4-39301605; COSMIC: COSV62899417; COSMIC: COSV62899417;