rs6586542

Variant names:

• chr1-17437070-G-C
• rs6586542
• NM_018715.4:c.285+1160C>G

Variant summary

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

The NM_018715.4(RCC2):​c.285+1160C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 152,090 control chromosomes in the GnomAD database, including 12,754 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 0.40 (12754 hom., cov: 33)
• Consequence: RCC2 NM_018715.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.265
• Publications: 9 publications found

Genes affected

RCC2 (HGNC:30297): (regulator of chromosome condensation 2) The protein encoded by this gene is a guanine exchange factor that is active on RalA, a small GTPase. The encoded protein and RalA are both essential for proper kinetochore-microtubule function in early mitosis. This protein has been shown to be a biomarker for colorectal cancer. [provided by RefSeq, Oct 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018715.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCC2	NM_018715.4	MANE Select	c.285+1160C>G		intron	N/A	NP_061185.1	A0A024RAC5
	RCC2	NM_001136204.3		c.285+1160C>G		intron	N/A	NP_001129676.1	Q9P258

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCC2	ENST00000375436.9	TSL:1 MANE Select	c.285+1160C>G		intron	N/A	ENSP00000364585.4	Q9P258
	RCC2	ENST00000375433.3	TSL:1	c.285+1160C>G		intron	N/A	ENSP00000364582.3	Q9P258
	RCC2	ENST00000927104.1		c.285+1160C>G		intron	N/A	ENSP00000597163.1

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60845 AN: 151972 Hom.: 12747 Cov.: 33

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.400 AC: 60908 AN: 152090 Hom.: 12754 Cov.: 33 AF XY: 0.403 AC XY: 30000 AN XY: 74354

African (AFR) AF: 0.525 AC: 21785 AN: 41472

American (AMR) AF: 0.384 AC: 5869 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 858 AN: 3472

East Asian (EAS) AF: 0.171 AC: 884 AN: 5176

South Asian (SAS) AF: 0.414 AC: 1999 AN: 4824

European-Finnish (FIN) AF: 0.398 AC: 4211 AN: 10578

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.357 AC: 24252 AN: 67976

Other (OTH) AF: 0.354 AC: 747 AN: 2110

Alfa AF: 0.383 Hom.: 1459

Bravo AF: 0.400

Asia WGS AF: 0.302 AC: 1054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.36
PhyloP100		0.27
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6586542;

hg19: chr1-17763566;