rs13147094

Variant names:

• chr4-39309262-G-A
• rs13147094
• NM_002913.5:c.1489-230C>T

Variant summary

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

The NM_002913.5(RFC1):​c.1489-230C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0936 in 152,010 control chromosomes in the GnomAD database, including 833 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 0.094 (833 hom., cov: 32)
• Consequence: RFC1 NM_002913.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102
• Publications: 6 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFC1	NM_002913.5	c.1489-230C>T		intron_variant	Intron 12 of 24	ENST00000349703.7	NP_002904.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RFC1	ENST00000349703.7	c.1489-230C>T		intron_variant	Intron 12 of 24	1	NM_002913.5	ENSP00000261424.4
RFC1	ENST00000381897.5	c.1489-230C>T		intron_variant	Intron 12 of 24	1		ENSP00000371321.1
RFC1	ENST00000504554.1	c.384+2183C>T		intron_variant	Intron 3 of 4	4		ENSP00000422129.1
RFC1	ENST00000502706.1	n.127-230C>T		intron_variant	Intron 2 of 4	5

Frequencies

GnomAD3 genomes AF: 0.0935 AC: 14208 AN: 151892 Hom.: 828 Cov.: 32

Gnomad AFR AF: 0.0280

Gnomad AMI AF: 0.0923

Gnomad AMR AF: 0.0882

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.0936 AC: 14222 AN: 152010 Hom.: 833 Cov.: 32 AF XY: 0.0937 AC XY: 6958 AN XY: 74278

African (AFR) AF: 0.0280 AC: 1162 AN: 41470

American (AMR) AF: 0.0882 AC: 1346 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 459 AN: 3468

East Asian (EAS) AF: 0.190 AC: 982 AN: 5168

South Asian (SAS) AF: 0.104 AC: 502 AN: 4816

European-Finnish (FIN) AF: 0.119 AC: 1255 AN: 10528

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8155 AN: 67984

Other (OTH) AF: 0.110 AC: 231 AN: 2104

Alfa AF: 0.107 Hom.: 398

Bravo AF: 0.0893

Asia WGS AF: 0.170 AC: 591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.52
PhyloP100		-0.10
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: rs13147094; hg19: chr4-39310882;