18-23168769-A-T

Variant names:

• chr18-23168769-A-T
• rs4800455
• NM_001100619.3:c.846-20069A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001100619.3(CABLES1):​c.846-20069A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000158 in 152,162 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00016 (0 hom., cov: 32)
• Consequence: CABLES1 NM_001100619.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.63
• Publications: 6 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100619.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CABLES1	NM_001100619.3	MANE Select	c.846-20069A>T		intron	N/A	NP_001094089.1	Q8TDN4-1
	CABLES1	NM_138375.3		c.50+12817A>T		intron	N/A	NP_612384.1	Q8TDN4-2
	CABLES1	NM_001256438.1		c.-136-20069A>T		intron	N/A	NP_001243367.1	Q8TDN4-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CABLES1	ENST00000256925.12	TSL:1 MANE Select	c.846-20069A>T		intron	N/A	ENSP00000256925.7	Q8TDN4-1
	CABLES1	ENST00000420687.2	TSL:1	c.50+12817A>T		intron	N/A	ENSP00000413851.2	Q8TDN4-2
	CABLES1	ENST00000877774.1		c.846-20069A>T		intron	N/A	ENSP00000547833.1

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152046 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152162 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74366

African (AFR) AF: 0.0000241 AC: 1 AN: 41500

American (AMR) AF: 0.000131 AC: 2 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 75284

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.062
DANN	Benign	0.31
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism

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: rs4800455; hg19: chr18-20748733;