chr10-118747172-C-T

Variant names:

• chr10-118747172-C-T
• rs4752195
• NM_153810.5:c.367+7224G>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.367+7224G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 152,112 control chromosomes in the GnomAD database, including 48,079 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 0.79 (48079 hom., cov: 32)
• Consequence: CACUL1 NM_153810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.791
• Publications: 1 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACUL1	NM_153810.5	c.367+7224G>A		intron_variant	Intron 1 of 8	ENST00000369151.8	NP_722517.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACUL1	ENST00000369151.8	c.367+7224G>A		intron_variant	Intron 1 of 8	1	NM_153810.5	ENSP00000358147.2
CACUL1	ENST00000477583.1	n.82+7224G>A		intron_variant	Intron 1 of 2	1
CACUL1	ENST00000493518.5	n.367+7224G>A		intron_variant	Intron 1 of 9	1		ENSP00000431329.1

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120728 AN: 151994 Hom.: 48039 Cov.: 32

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.852

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.823

Gnomad OTH AF: 0.798

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

GnomAD4 genome AF: 0.794 AC: 120823 AN: 152112 Hom.: 48079 Cov.: 32 AF XY: 0.793 AC XY: 58952 AN XY: 74370

African (AFR) AF: 0.748 AC: 31029 AN: 41476

American (AMR) AF: 0.828 AC: 12667 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.852 AC: 2957 AN: 3470

East Asian (EAS) AF: 0.704 AC: 3650 AN: 5182

South Asian (SAS) AF: 0.780 AC: 3756 AN: 4816

European-Finnish (FIN) AF: 0.774 AC: 8189 AN: 10574

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.823 AC: 55923 AN: 67986

Other (OTH) AF: 0.794 AC: 1677 AN: 2112

Alfa AF: 0.813 Hom.: 25778

Bravo AF: 0.794

Asia WGS AF: 0.755 AC: 2624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.28
DANN	Benign	0.74
PhyloP100		-0.79
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: rs4752195; hg19: chr10-120506684;