1-17411671-T-C

Variant summary

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

The NM_018715.4(RCC2):c.1386+451A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 152,098 control chromosomes in the GnomAD database, including 57,166 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 0.86 (57166 hom., cov: 30)
• Consequence: RCC2 NM_018715.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RCC2	NM_018715.4	c.1386+451A>G		intron_variant		ENST00000375436.9
RCC2	NM_001136204.3	c.1386+451A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RCC2	ENST00000375436.9	c.1386+451A>G		intron_variant		1	NM_018715.4	P1
RCC2	ENST00000375433.3	c.1386+451A>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131350 AN: 151984 Hom.: 57100 Cov.: 30

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.897

Gnomad FIN AF: 0.790

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.845

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

GnomAD4 genome AF: 0.864 AC: 131474 AN: 152098 Hom.: 57166 Cov.: 30 AF XY: 0.865 AC XY: 64265 AN XY: 74316

Gnomad4 AFR AF: 0.968

Gnomad4 AMR AF: 0.851

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.814

Gnomad4 SAS AF: 0.897

Gnomad4 FIN AF: 0.790

Gnomad4 NFE AF: 0.824

Gnomad4 OTH AF: 0.847

Alfa AF: 0.840 Hom.: 40956

Bravo AF: 0.872

Asia WGS AF: 0.892 AC: 3102 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.5
Dann	Benign	0.36

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: rs1204897; hg19: chr1-17738167;