10-118704208-G-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACUL1	NM_153810.5	c.694-2800C>A		intron_variant	Intron 4 of 8	ENST00000369151.8	NP_722517.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACUL1	ENST00000369151.8	c.694-2800C>A		intron_variant	Intron 4 of 8	1	NM_153810.5	ENSP00000358147.2
CACUL1	ENST00000493518.5	n.694-2800C>A		intron_variant	Intron 4 of 9	1		ENSP00000431329.1
CACUL1	ENST00000481360.1	n.23-2800C>A		intron_variant	Intron 1 of 2	5
CACUL1	ENST00000544392.5	n.205-2800C>A		intron_variant	Intron 2 of 7	2

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

Gnomad4 AFR AF: 0.751

Gnomad4 AMR AF: 0.830

Gnomad4 ASJ AF: 0.851

Gnomad4 EAS AF: 0.706

Gnomad4 SAS AF: 0.781

Gnomad4 FIN AF: 0.781

Gnomad4 NFE AF: 0.823

Gnomad4 OTH AF: 0.793

Alfa AF: 0.820 Hom.: 44229

Bravo AF: 0.794

Asia WGS AF: 0.747 AC: 2596 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.63
DANN	Benign	0.17

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: rs10886289; hg19: chr10-120463720;