18-23147647-C-T

Variant summary

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

The NM_001100619.3(CABLES1):c.845+11040C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 152,196 control chromosomes in the GnomAD database, including 41,659 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 0.74 (41659 hom., cov: 33)
• Consequence: CABLES1 NM_001100619.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

Genes affected

CABLES1 (HGNC:25097): (Cdk5 and Abl enzyme substrate 1) This gene encodes a protein involved in regulation of the cell cycle through interactions with several cyclin-dependent kinases. One study (PMID: 16177568) reported aberrant splicing of transcripts from this gene which results in removal of the cyclin binding domain only in human cancer cells, and reduction in gene expression was shown in colorectal cancers (PMID: 17982127).Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CABLES1	NM_001100619.3	c.845+11040C>T		intron_variant		ENST00000256925.12
CABLES1	NM_001256438.1	c.-137+12977C>T		intron_variant
CABLES1	NR_023359.2	n.88+12996C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CABLES1	ENST00000256925.12	c.845+11040C>T		intron_variant		1	NM_001100619.3

Frequencies

GnomAD3 genomes AF: 0.736 AC: 111937 AN: 152078 Hom.: 41660 Cov.: 33

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.868

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.843

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.814

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.753

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

GnomAD4 genome AF: 0.736 AC: 111975 AN: 152196 Hom.: 41659 Cov.: 33 AF XY: 0.735 AC XY: 54718 AN XY: 74418

Gnomad4 AFR AF: 0.648

Gnomad4 AMR AF: 0.630

Gnomad4 ASJ AF: 0.843

Gnomad4 EAS AF: 0.806

Gnomad4 SAS AF: 0.814

Gnomad4 FIN AF: 0.776

Gnomad4 NFE AF: 0.788

Gnomad4 OTH AF: 0.752

Alfa AF: 0.782 Hom.: 85775

Bravo AF: 0.720

Asia WGS AF: 0.805 AC: 2801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.23
Dann	Benign	0.82

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: rs4800452; hg19: chr18-20727611;