Variant 4-39300409-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000349703.7(RFC1):c.2541A>G(p.Pro847=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 1,611,612 control chromosomes in the GnomAD database, including 253,413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 18661 hom., cov: 32)

Exomes 𝑓: 0.56 ( 234752 hom. )

Consequence

RFC1
ENST00000349703.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.95

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 4-39300409-T-C is Benign according to our data. Variant chr4-39300409-T-C is described in ClinVar as [Benign]. Clinvar id is 1327949.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.95 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.617 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.2541A>G	p.Pro847=	synonymous_variant	20/25	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.2541A>G	p.Pro847=	synonymous_variant	20/25	1	NM_002913.5	ENSP00000261424	P4	P35251-2
RFC1	ENST00000381897.5 linkuse as main transcript	c.2544A>G	p.Pro848=	synonymous_variant	20/25	1		ENSP00000371321	A2	P35251-1
RFC1	ENST00000505077.1 linkuse as main transcript	n.473A>G		non_coding_transcript_exon_variant	5/5	4

Frequencies

GnomAD3 genomes

AF:

0.454

AC:

68910

AN:

151892

Hom.:

18663

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.541

Gnomad AMR

AF:

0.583

Gnomad ASJ

AF:

0.529

Gnomad EAS

AF:

0.636

Gnomad SAS

AF:

0.615

Gnomad FIN

AF:

0.545

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.570

Gnomad OTH

AF:

0.484

GnomAD3 exomes

AF:

0.558

AC:

140006

AN:

250688

Hom.:

41046

AF XY:

0.565

AC XY:

76522

AN XY:

135474

show subpopulations

Gnomad AFR exome

AF:

0.128

Gnomad AMR exome

AF:

0.660

Gnomad ASJ exome

AF:

0.532

Gnomad EAS exome

AF:

0.655

Gnomad SAS exome

AF:

0.595

Gnomad FIN exome

AF:

0.548

Gnomad NFE exome

AF:

0.568

Gnomad OTH exome

AF:

0.564

GnomAD4 exome

AF:

0.562

AC:

819854

AN:

1459602

Hom.:

234752

Cov.:

AF XY:

0.564

AC XY:

409464

AN XY:

726176

show subpopulations

Gnomad4 AFR exome

AF:

0.123

Gnomad4 AMR exome

AF:

0.645

Gnomad4 ASJ exome

AF:

0.539

Gnomad4 EAS exome

AF:

0.644

Gnomad4 SAS exome

AF:

0.593

Gnomad4 FIN exome

AF:

0.554

Gnomad4 NFE exome

AF:

0.568

Gnomad4 OTH exome

AF:

0.541

GnomAD4 genome

AF:

0.453

AC:

68904

AN:

152010

Hom.:

18661

Cov.:

AF XY:

0.459

AC XY:

34083

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.139

Gnomad4 AMR

AF:

0.583

Gnomad4 ASJ

AF:

0.529

Gnomad4 EAS

AF:

0.635

Gnomad4 SAS

AF:

0.615

Gnomad4 FIN

AF:

0.545

Gnomad4 NFE

AF:

0.570

Gnomad4 OTH

AF:

0.483

Alfa

AF:

0.536

Hom.:

28155

Bravo

AF:

0.441

Asia WGS

AF:

0.577

AC:

2009

AN:

3478

EpiCase

AF:

0.570

EpiControl

AF:

0.571

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

RFC1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 30, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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

-0.78

CADD

Benign

3.5

DANN

Benign

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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