4-39335333-A-G

Position:

• chr4-39335333-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.331+7012T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,000 control chromosomes in the GnomAD database, including 8,045 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 0.32 (8045 hom., cov: 31)
• Consequence: RFC1 NM_002913.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

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=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RFC1	NM_002913.5	c.331+7012T>C		intron_variant		ENST00000349703.7	NP_002904.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFC1	ENST00000349703.7	c.331+7012T>C		intron_variant		1	NM_002913.5	ENSP00000261424	P4

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48767 AN: 151882 Hom.: 8041 Cov.: 31

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.309

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.321 AC: 48780 AN: 152000 Hom.: 8045 Cov.: 31 AF XY: 0.319 AC XY: 23674 AN XY: 74284

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.305

Alfa AF: 0.345 Hom.: 4278

Bravo AF: 0.308

Asia WGS AF: 0.233 AC: 810 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.5
DANN	Benign	0.89

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: rs3796517; hg19: chr4-39336953;