rs4752194

Positions:

• chr10-118735652-C-A
• chr10-118735652-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153810.5(CACUL1):​c.368-5242G>T 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 152,032 control chromosomes in the GnomAD database, including 48,062 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 (48062 hom., cov: 31)
• Consequence: CACUL1 NM_153810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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=-0.93).
• 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/exons	MANE	Protein	UniProt
CACUL1	NM_153810.5	c.368-5242G>T		intron_variant		ENST00000369151.8	NP_722517.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACUL1	ENST00000369151.8	c.368-5242G>T		intron_variant		1	NM_153810.5	ENSP00000358147	P1
CACUL1	ENST00000493518.5	c.368-5242G>T		intron_variant, NMD_transcript_variant		1		ENSP00000431329
CACUL1	ENST00000477583.1	n.83-5242G>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120679 AN: 151914 Hom.: 48022 Cov.: 31

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.852

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.775

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: 120774 AN: 152032 Hom.: 48062 Cov.: 31 AF XY: 0.793 AC XY: 58893 AN XY: 74294

Gnomad4 AFR AF: 0.748

Gnomad4 AMR AF: 0.829

Gnomad4 ASJ AF: 0.852

Gnomad4 EAS AF: 0.702

Gnomad4 SAS AF: 0.778

Gnomad4 FIN AF: 0.775

Gnomad4 NFE AF: 0.823

Gnomad4 OTH AF: 0.795

Alfa AF: 0.815 Hom.: 26956

Bravo AF: 0.794

Asia WGS AF: 0.754 AC: 2621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	10
DANN	Benign	0.33

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: rs4752194; hg19: chr10-120495164;