rs11096991

Positions:

• chr4-39319011-T-C

Variant summary

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

The ENST00000349703.7(RFC1):​c.1095+1372A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,088 control chromosomes in the GnomAD database, including 8,424 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 0.33 (8424 hom., cov: 32)
• Consequence: RFC1 ENST00000349703.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RFC1	NM_002913.5	c.1095+1372A>G		intron_variant		ENST00000349703.7	NP_002904.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFC1	ENST00000349703.7	c.1095+1372A>G		intron_variant		1	NM_002913.5	ENSP00000261424	P4
RFC1	ENST00000381897.5	c.1095+1372A>G		intron_variant		1		ENSP00000371321	A2
RFC1	ENST00000512881.5	n.497+1372A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50096 AN: 151970 Hom.: 8420 Cov.: 32

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.329 AC: 50112 AN: 152088 Hom.: 8424 Cov.: 32 AF XY: 0.327 AC XY: 24273 AN XY: 74314

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.409

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.313

Alfa AF: 0.346 Hom.: 1870

Bravo AF: 0.318

Asia WGS AF: 0.231 AC: 802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.7
DANN	Benign	0.57

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: rs11096991; hg19: chr4-39320631;