Variant chr4-39342320-C-A 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.331+25G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 1,600,238 control chromosomes in the GnomAD database, including 217,605 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 16258 hom., cov: 31)

Exomes 𝑓: 0.52 ( 201347 hom. )

Consequence

RFC1
NM_002913.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.394

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:

RFC1 (HGNC:):

RFC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 4-39342320-C-A is Benign according to our data. Variant chr4-39342320-C-A is described in ClinVar as [Benign]. Clinvar id is 1327950.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.61 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.331+25G>T		intron_variant		ENST00000349703.7	NP_002904.3	P35251-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFC1	ENST00000349703.7 linkuse as main transcript	c.331+25G>T		intron_variant		1	NM_002913.5	ENSP00000261424.4		P35251-2

Frequencies

GnomAD3 genomes

AF:

0.423

AC:

64208

AN:

151798

Hom.:

16255

Cov.:

show subpopulations

Gnomad AFR

AF:

0.130

Gnomad AMI

AF:

0.555

Gnomad AMR

AF:

0.567

Gnomad ASJ

AF:

0.506

Gnomad EAS

AF:

0.629

Gnomad SAS

AF:

0.581

Gnomad FIN

AF:

0.476

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.526

Gnomad OTH

AF:

0.463

GnomAD3 exomes

AF:

0.524

AC:

130149

AN:

248444

Hom.:

35997

AF XY:

0.529

AC XY:

71034

AN XY:

134236

show subpopulations

Gnomad AFR exome

AF:

0.121

Gnomad AMR exome

AF:

0.645

Gnomad ASJ exome

AF:

0.509

Gnomad EAS exome

AF:

0.645

Gnomad SAS exome

AF:

0.563

Gnomad FIN exome

AF:

0.472

Gnomad NFE exome

AF:

0.526

Gnomad OTH exome

AF:

0.529

GnomAD4 exome

AF:

0.521

AC:

755065

AN:

1448322

Hom.:

201347

Cov.:

AF XY:

0.523

AC XY:

376993

AN XY:

720422

show subpopulations

Gnomad4 AFR exome

AF:

0.116

Gnomad4 AMR exome

AF:

0.632

Gnomad4 ASJ exome

AF:

0.514

Gnomad4 EAS exome

AF:

0.637

Gnomad4 SAS exome

AF:

0.558

Gnomad4 FIN exome

AF:

0.476

Gnomad4 NFE exome

AF:

0.526

Gnomad4 OTH exome

AF:

0.498

GnomAD4 genome

AF:

0.423

AC:

64208

AN:

151916

Hom.:

16258

Cov.:

AF XY:

0.429

AC XY:

31864

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.130

Gnomad4 AMR

AF:

0.567

Gnomad4 ASJ

AF:

0.506

Gnomad4 EAS

AF:

0.628

Gnomad4 SAS

AF:

0.581

Gnomad4 FIN

AF:

0.476

Gnomad4 NFE

AF:

0.526

Gnomad4 OTH

AF:

0.463

Alfa

AF:

0.500

Hom.:

10188

Bravo

AF:

0.417

Asia WGS

AF:

0.556

AC:

1934

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

-0.81

CADD

Benign

3.9

DANN

Benign

0.74

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