rs6851075

Variant names:

• chr4-39366034-T-C
• rs6851075
• NM_002913.5:c.3+205A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-39366034-T-C
• chr4-39366034-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002913.5(RFC1):​c.3+205A>G 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 150,178 control chromosomes in the GnomAD database, including 7,694 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 (7694 hom., cov: 32)
• Consequence: RFC1 NM_002913.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• cerebellar ataxia, neuropathy, and vestibular areflexia syndrome

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFC1	NM_002913.5	c.3+205A>G		intron_variant	Intron 1 of 24	ENST00000349703.7	NP_002904.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RFC1	ENST00000349703.7	c.3+205A>G		intron_variant	Intron 1 of 24	1	NM_002913.5	ENSP00000261424.4

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48158 AN: 150066 Hom.: 7689 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.321 AC: 48164 AN: 150178 Hom.: 7694 Cov.: 32 AF XY: 0.317 AC XY: 23243 AN XY: 73298

African (AFR) AF: 0.321 AC: 13250 AN: 41240

American (AMR) AF: 0.282 AC: 4271 AN: 15124

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1212 AN: 3442

East Asian (EAS) AF: 0.171 AC: 833 AN: 4884

South Asian (SAS) AF: 0.313 AC: 1445 AN: 4624

European-Finnish (FIN) AF: 0.353 AC: 3619 AN: 10258

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22467 AN: 67310

Other (OTH) AF: 0.315 AC: 661 AN: 2096

Alfa AF: 0.327 Hom.: 13801

Bravo AF: 0.313

Asia WGS AF: 0.226 AC: 786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.42
DANN	Benign	0.66
PhyloP100		-1.8
PromoterAI		-0.068	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6851075; hg19: chr4-39367654;