18-23155444-T-C

Variant names:

• chr18-23155444-T-C
• rs4369779
• NM_001100619.3:c.845+18837T>C

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+18837T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,184 control chromosomes in the GnomAD database, including 46,581 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 0.78 (46581 hom., cov: 33)
• Consequence: CABLES1 NM_001100619.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.113
• Publications: 45 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

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.845+18837T>C		intron	N/A	NP_001094089.1	Q8TDN4-1
	CABLES1	NM_001256438.1		c.-137+20774T>C		intron	N/A	NP_001243367.1	Q8TDN4-4
	CABLES1	NR_023359.2		n.88+20793T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CABLES1	ENST00000256925.12	TSL:1 MANE Select	c.845+18837T>C		intron	N/A	ENSP00000256925.7	Q8TDN4-1
	CABLES1	ENST00000877774.1		c.845+18837T>C		intron	N/A	ENSP00000547833.1
	CABLES1	ENST00000952329.1		c.845+18837T>C		intron	N/A	ENSP00000622388.1

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118648 AN: 152066 Hom.: 46543 Cov.: 33

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.870

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.874

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.792

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

GnomAD4 genome AF: 0.780 AC: 118740 AN: 152184 Hom.: 46581 Cov.: 33 AF XY: 0.779 AC XY: 57980 AN XY: 74396

African (AFR) AF: 0.784 AC: 32558 AN: 41526

American (AMR) AF: 0.652 AC: 9975 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.874 AC: 3034 AN: 3472

East Asian (EAS) AF: 0.835 AC: 4320 AN: 5176

South Asian (SAS) AF: 0.845 AC: 4077 AN: 4826

European-Finnish (FIN) AF: 0.777 AC: 8214 AN: 10574

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.792 AC: 53841 AN: 68004

Other (OTH) AF: 0.792 AC: 1673 AN: 2112

Alfa AF: 0.795 Hom.: 166812

Bravo AF: 0.769

Asia WGS AF: 0.849 AC: 2951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.9
DANN	Benign	0.71
PhyloP100		0.11
PromoterAI		0.0065	Neutral
Mutation Taster		=98/2	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: rs4369779; hg19: chr18-20735408;