Genetic Variant RFC1:c.-222G>A (chr4-39366463-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002913.5(RFC1):c.-222G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 472,634 control chromosomes in the GnomAD database, including 55,970 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.45 ( 16109 hom., cov: 31)

Exomes 𝑓: 0.49 ( 39861 hom. )

Consequence

RFC1
NM_002913.5 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.757

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 -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFC1	NM_002913.5 link	c.-222G>A		upstream_gene_variant		ENST00000349703.7	NP_002904.3	P35251-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RFC1	ENST00000349703.7 link	c.-222G>A		upstream_gene_variant		1	NM_002913.5	ENSP00000261424.4		P35251-2

Frequencies

GnomAD3 genomes

AF:

0.453

AC:

68724

AN:

151768

Hom.:

16102

Cov.:

show subpopulations

Gnomad AFR

AF:

0.355

Gnomad AMI

AF:

0.595

Gnomad AMR

AF:

0.404

Gnomad ASJ

AF:

0.432

Gnomad EAS

AF:

0.451

Gnomad SAS

AF:

0.420

Gnomad FIN

AF:

0.584

Gnomad MID

AF:

0.420

Gnomad NFE

AF:

0.505

Gnomad OTH

AF:

0.448

GnomAD4 exome

AF:

0.495

AC:

158690

AN:

320748

Hom.:

39861

AF XY:

0.493

AC XY:

82107

AN XY:

166504

show subpopulations

Gnomad4 AFR exome

AF:

0.368

Gnomad4 AMR exome

AF:

0.425

Gnomad4 ASJ exome

AF:

0.424

Gnomad4 EAS exome

AF:

0.441

Gnomad4 SAS exome

AF:

0.457

Gnomad4 FIN exome

AF:

0.580

Gnomad4 NFE exome

AF:

0.507

Gnomad4 OTH exome

AF:

0.486

GnomAD4 genome

AF:

0.453

AC:

68743

AN:

151886

Hom.:

16109

Cov.:

AF XY:

0.452

AC XY:

33561

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.354

Gnomad4 AMR

AF:

0.403

Gnomad4 ASJ

AF:

0.432

Gnomad4 EAS

AF:

0.451

Gnomad4 SAS

AF:

0.420

Gnomad4 FIN

AF:

0.584

Gnomad4 NFE

AF:

0.505

Gnomad4 OTH

AF:

0.449

Alfa

AF:

0.470

Hom.:

2098

Bravo

AF:

0.436

Asia WGS

AF:

0.480

AC:

1668

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.3

DANN

Benign

0.90

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over