18-23147647-C-T

Variant names:

• chr18-23147647-C-T
• rs4800452
• NM_001100619.3:c.845+11040C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 47 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CABLES1	NM_001100619.3	c.845+11040C>T		intron_variant	Intron 1 of 9	ENST00000256925.12	NP_001094089.1
CABLES1	NM_001256438.1	c.-137+12977C>T		intron_variant	Intron 1 of 9		NP_001243367.1
CABLES1	NR_023359.2	n.88+12996C>T		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CABLES1	ENST00000256925.12	c.845+11040C>T		intron_variant	Intron 1 of 9	1	NM_001100619.3	ENSP00000256925.7

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

African (AFR) AF: 0.648 AC: 26906 AN: 41528

American (AMR) AF: 0.630 AC: 9627 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 2926 AN: 3472

East Asian (EAS) AF: 0.806 AC: 4178 AN: 5182

South Asian (SAS) AF: 0.814 AC: 3929 AN: 4828

European-Finnish (FIN) AF: 0.776 AC: 8223 AN: 10602

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.788 AC: 53566 AN: 67980

Other (OTH) AF: 0.752 AC: 1589 AN: 2112

Alfa AF: 0.773 Hom.: 172783

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
PhyloP100		-1.2
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: rs4800452; hg19: chr18-20727611;