1-28530610-G-C

Variant names:

• chr1-28530610-G-C
• rs780561548
• ENST00000373831.7:c.161G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001381865.2(RCC1):​c.73+671G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000551 in 1,450,998 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: RCC1 NM_001381865.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.564
• Publications: 0 publications found

Genes affected

RCC1 (HGNC:1913): (regulator of chromosome condensation 1) Enables several functions, including guanyl-nucleotide exchange factor activity; nucleosomal DNA binding activity; and protein heterodimerization activity. Involved in several processes, including G1/S transition of mitotic cell cycle; regulation of mitotic nuclear division; and spindle organization. Located in chromatin; cytoplasm; and nucleus. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.115024894).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCC1	NM_001381865.2	c.73+671G>C		intron_variant	Intron 5 of 12	ENST00000683442.1	NP_001368794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCC1	ENST00000683442.1	c.73+671G>C		intron_variant	Intron 5 of 12		NM_001381865.2	ENSP00000508074.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000438 AC: 1 AN: 228296 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000968

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000551 AC: 8 AN: 1450998 Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 2 AN XY: 722212

African (AFR) AF: 0.00 AC: 0 AN: 33412

American (AMR) AF: 0.00 AC: 0 AN: 44556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25988

East Asian (EAS) AF: 0.00 AC: 0 AN: 39616

South Asian (SAS) AF: 0.00 AC: 0 AN: 85982

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44872

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5644

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1110778

Other (OTH) AF: 0.00 AC: 0 AN: 60150

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000845 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000594

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	13
DANN	Benign	0.86
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.32	.;T
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.1	T
PhyloP100		0.56
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.25	.;N
REVEL	Benign	0.020
Sift	Benign	0.25	.;T
Sift4G	Benign	0.29	.;T
Polyphen		0.48	P;P
Vest4		0.40
MutPred		0.34		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.27
MPC		0.73
ClinPred		0.21	T
GERP RS		1.4
gMVP		0.34
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs780561548; hg19: chr1-28857122;