Variant 3-186790133-C-T 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 ENST00000296273.7(RFC4):c.996+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,605,322 control chromosomes in the GnomAD database, including 56,171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4952 hom., cov: 32)

Exomes 𝑓: 0.26 ( 51219 hom. )

Consequence

RFC4
ENST00000296273.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.82

Variant links:

Genes affected

RFC4 (HGNC:9972): (replication factor C subunit 4) The elongation of primed DNA templates by DNA polymerase delta and DNA polymerase epsilon requires the accessory proteins proliferating cell nuclear antigen (PCNA) and replication factor C (RFC). RFC, also named activator 1, is a protein complex consisting of five distinct subunits of 140, 40, 38, 37, and 36 kD. This gene encodes the 37 kD subunit. This subunit forms a core complex with the 36 and 40 kDa subunits. The core complex possesses DNA-dependent ATPase activity, which was found to be stimulated by PCNA in an in vitro system. Alternatively spliced transcript variants encoding the same protein have been reported. [provided by RefSeq, Jul 2008]

RFC4 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=-0.59).

BP6

Variant 3-186790133-C-T is Benign according to our data. Variant chr3-186790133-C-T is described in ClinVar as [Benign]. Clinvar id is 1268726.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RFC4	NM_002916.5 linkuse as main transcript	c.996+9G>A		intron_variant		ENST00000296273.7	NP_002907.1
RFC4	NM_181573.3 linkuse as main transcript	c.996+9G>A		intron_variant			NP_853551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFC4	ENST00000296273.7 linkuse as main transcript	c.996+9G>A		intron_variant		1	NM_002916.5	ENSP00000296273	P1	P35249-1

Frequencies

GnomAD3 genomes

AF:

0.235

AC:

35751

AN:

151878

Hom.:

4947

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.284

Gnomad AMR

AF:

0.331

Gnomad ASJ

AF:

0.227

Gnomad EAS

AF:

0.410

Gnomad SAS

AF:

0.308

Gnomad FIN

AF:

0.404

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.247

Gnomad OTH

AF:

0.225

GnomAD3 exomes

AF:

0.293

AC:

73376

AN:

250628

Hom.:

11792

AF XY:

0.288

AC XY:

38943

AN XY:

135396

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.425

Gnomad ASJ exome

AF:

0.214

Gnomad EAS exome

AF:

0.399

Gnomad SAS exome

AF:

0.292

Gnomad FIN exome

AF:

0.398

Gnomad NFE exome

AF:

0.250

Gnomad OTH exome

AF:

0.286

GnomAD4 exome

AF:

0.259

AC:

375932

AN:

1453326

Hom.:

51219

Cov.:

AF XY:

0.259

AC XY:

187280

AN XY:

723394

show subpopulations

Gnomad4 AFR exome

AF:

0.0989

Gnomad4 AMR exome

AF:

0.419

Gnomad4 ASJ exome

AF:

0.219

Gnomad4 EAS exome

AF:

0.413

Gnomad4 SAS exome

AF:

0.290

Gnomad4 FIN exome

AF:

0.393

Gnomad4 NFE exome

AF:

0.244

Gnomad4 OTH exome

AF:

0.257

GnomAD4 genome

AF:

0.235

AC:

35770

AN:

151996

Hom.:

4952

Cov.:

AF XY:

0.245

AC XY:

18209

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.108

Gnomad4 AMR

AF:

0.332

Gnomad4 ASJ

AF:

0.227

Gnomad4 EAS

AF:

0.410

Gnomad4 SAS

AF:

0.308

Gnomad4 FIN

AF:

0.404

Gnomad4 NFE

AF:

0.247

Gnomad4 OTH

AF:

0.225

Alfa

AF:

0.240

Hom.:

8032

Bravo

AF:

0.225

Asia WGS

AF:

0.376

AC:

1310

AN:

3478

EpiCase

AF:

0.236

EpiControl

AF:

0.239

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.0010

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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