Variant 4-39299985-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.21

Variant links:

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]

RFC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
RFC1	NM_002913.5 linkuse as main transcript	c.2808+36C>G		intron_variant		ENST00000349703.7	NP_002904.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFC1	ENST00000349703.7 linkuse as main transcript	c.2808+36C>G		intron_variant		1	NM_002913.5	ENSP00000261424	P4	P35251-2
RFC1	ENST00000381897.5 linkuse as main transcript	c.2811+36C>G		intron_variant		1		ENSP00000371321	A2	P35251-1

Frequencies

GnomAD3 genomes

AF:

0.512

AC:

77788

AN:

152034

Hom.:

21640

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.435

AC XY:

237170

AN XY:

545288

show subpopulations

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.:

AF XY:

0.507

AC XY:

37686

AN XY:

74352

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over