chr1-17411671-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0780

Publications

4 publications found
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank MANE Protein UniProt
RCC2NM_018715.4 linkc.1386+451A>G intron_variant Intron 11 of 12 ENST00000375436.9 NP_061185.1 Q9P258A0A024RAC5
RCC2NM_001136204.3 linkc.1386+451A>G intron_variant Intron 10 of 11 NP_001129676.1 Q9P258A0A024RAC5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RCC2ENST00000375436.9 linkc.1386+451A>G intron_variant Intron 11 of 12 1 NM_018715.4 ENSP00000364585.4 Q9P258
RCC2ENST00000375433.3 linkc.1386+451A>G intron_variant Intron 10 of 11 1 ENSP00000364582.3 Q9P258

Frequencies

GnomAD3 genomes
AF:
0.864
AC:
131350
AN:
151984
Hom.:
57100
Cov.:
30
show subpopulations
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
show subpopulations
African (AFR)
AF:
0.968
AC:
40204
AN:
41514
American (AMR)
AF:
0.851
AC:
12994
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
0.762
AC:
2640
AN:
3466
East Asian (EAS)
AF:
0.814
AC:
4201
AN:
5158
South Asian (SAS)
AF:
0.897
AC:
4321
AN:
4816
European-Finnish (FIN)
AF:
0.790
AC:
8327
AN:
10536
Middle Eastern (MID)
AF:
0.864
AC:
254
AN:
294
European-Non Finnish (NFE)
AF:
0.824
AC:
56069
AN:
68020
Other (OTH)
AF:
0.847
AC:
1785
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.509
Heterozygous variant carriers
0
896
1792
2687
3583
4479
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
894
1788
2682
3576
4470
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.840
Hom.:
55287
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
PhyloP100
-0.078
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

Publications

Other links and lift over

dbSNP: rs1204897; hg19: chr1-17738167; API