10-118704208-G-T

Variant names:

• chr10-118704208-G-T
• rs10886289
• NM_153810.5:c.694-2800C>A

Variant summary

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

The NM_153810.5(CACUL1):​c.694-2800C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 150,558 control chromosomes in the GnomAD database, including 47,777 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 0.80 (47777 hom., cov: 26)
• Consequence: CACUL1 NM_153810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 5 publications found

Genes affected

CACUL1 (HGNC:23727): (CDK2 associated cullin domain 1) Enables protein kinase binding activity. Involved in G1/S transition of mitotic cell cycle; positive regulation of cell population proliferation; and positive regulation of protein kinase activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153810.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACUL1	NM_153810.5	MANE Select	c.694-2800C>A		intron	N/A	NP_722517.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACUL1	ENST00000369151.8	TSL:1 MANE Select	c.694-2800C>A		intron	N/A	ENSP00000358147.2
	CACUL1	ENST00000493518.5	TSL:1	n.694-2800C>A		intron	N/A	ENSP00000431329.1
	CACUL1	ENST00000481360.1	TSL:5	n.23-2800C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.796 AC: 119824 AN: 150452 Hom.: 47739 Cov.: 26

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.781

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.823

Gnomad OTH AF: 0.796

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

GnomAD4 genome AF: 0.796 AC: 119913 AN: 150558 Hom.: 47777 Cov.: 26 AF XY: 0.795 AC XY: 58393 AN XY: 73444

African (AFR) AF: 0.751 AC: 30698 AN: 40854

American (AMR) AF: 0.830 AC: 12593 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 2953 AN: 3468

East Asian (EAS) AF: 0.706 AC: 3619 AN: 5124

South Asian (SAS) AF: 0.781 AC: 3697 AN: 4732

European-Finnish (FIN) AF: 0.781 AC: 7960 AN: 10188

Middle Eastern (MID) AF: 0.825 AC: 241 AN: 292

European-Non Finnish (NFE) AF: 0.823 AC: 55767 AN: 67732

Other (OTH) AF: 0.793 AC: 1660 AN: 2094

Alfa AF: 0.818 Hom.: 53344

Bravo AF: 0.794

Asia WGS AF: 0.747 AC: 2596 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.63
DANN	Benign	0.17
PhyloP100		-1.4
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: rs10886289; hg19: chr10-120463720;