rs4975003

Variant names:

• chr4-39311850-G-A
• rs4975003
• NM_002913.5:c.1384-301C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-39311850-G-A
• chr4-39311850-G-C
• chr4-39311850-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002913.5(RFC1):​c.1384-301C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 151,964 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00011 (0 hom., cov: 32)
• Consequence: RFC1 NM_002913.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105
• Publications: 3 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFC1	NM_002913.5	c.1384-301C>T		intron_variant	Intron 11 of 24	ENST00000349703.7	NP_002904.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RFC1	ENST00000349703.7	c.1384-301C>T		intron_variant	Intron 11 of 24	1	NM_002913.5	ENSP00000261424.4
RFC1	ENST00000381897.5	c.1384-301C>T		intron_variant	Intron 11 of 24	1		ENSP00000371321.1
RFC1	ENST00000504554.1	c.280-301C>T		intron_variant	Intron 2 of 4	4		ENSP00000422129.1
RFC1	ENST00000502706.1	n.22-301C>T		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 151964 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000112 AC: 17 AN: 151964 Hom.: 0 Cov.: 32 AF XY: 0.0000943 AC XY: 7 AN XY: 74214

African (AFR) AF: 0.0000484 AC: 2 AN: 41344

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 67982

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 934

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.4
DANN	Benign	0.52
PhyloP100		0.10

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: rs4975003; hg19: chr4-39313470;