4-39287853-A-G

Position:

• chr4-39287853-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002913.5(RFC1):​c.*908T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 151,980 control chromosomes in the GnomAD database, including 23,247 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 0.53 (23245 hom., cov: 31)
  • Exomes 𝑓: 0.44 (2 hom.)
• Consequence: RFC1 NM_002913.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.464

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RFC1	NM_002913.5	c.*908T>C		3_prime_UTR_variant	25/25	ENST00000349703.7	NP_002904.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFC1	ENST00000349703	c.*908T>C		3_prime_UTR_variant	25/25	1	NM_002913.5	ENSP00000261424.4
RFC1	ENST00000381897	c.*908T>C		3_prime_UTR_variant	25/25	1		ENSP00000371321.1

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79929 AN: 151846 Hom.: 23205 Cov.: 31

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.501

GnomAD4 exome AF: 0.438 AC: 7 AN: 16 Hom.: 2 Cov.: 0 AF XY: 0.429 AC XY: 6 AN XY: 14

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 NFE exome AF: 0.417

GnomAD4 genome AF: 0.527 AC: 80030 AN: 151964 Hom.: 23245 Cov.: 31 AF XY: 0.521 AC XY: 38689 AN XY: 74264

Gnomad4 AFR AF: 0.788

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.502

Alfa AF: 0.447 Hom.: 15355

Bravo AF: 0.535

Asia WGS AF: 0.430 AC: 1495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.41
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

Other links and lift over

dbSNP: rs1057807; hg19: chr4-39289473;